1. {{On alert for autism spectrum disorders}}. {Nursing};2013 (Apr);43(4):34-35.
Lien vers le texte intégral (Open Access ou abonnement)
2. Amiet C, Gourfinkel-An I, Laurent C, Carayol J, Genin B, Leguern E, Tordjman S, Cohen D. {{Epilepsy in Simplex Autism Pedigrees Is Much Lower Than the Rate in Multiplex Autism Pedigrees}}. {Biol Psychiatry};2013 (Mar 15)
Lien vers le texte intégral (Open Access ou abonnement)
3. Bahl S, Chiang C, Beauchamp RL, Neale BM, Daly MJ, Gusella JF, Talkowski ME, Ramesh V. {{Lack of association of rare functional variants in TSC1/TSC2 genes with autism spectrum disorder}}. {Mol Autism};2013 (Mar 20);4(1):5.
BACKGROUND: Autism spectrum disorder (ASD) is reported in 30 to 60% of patients with tuberous sclerosis complex (TSC) but shared genetic mechanisms that exist between TSC-associated ASD and idiopathic ASD have yet to be determined. Through the small G-protein Rheb, the TSC proteins, hamartin and tuberin, negatively regulate mammalian target of rapamycin complex 1 (mTORC1) signaling. It is well established that mTORC1 plays a pivotal role in neuronal translation and connectivity, so dysregulation of mTORC1 signaling could be a common feature in many ASDs. Pam, an E3 ubiquitin ligase, binds to TSC proteins and regulates mTORC1 signaling in the CNS, and the FBXO45-Pam ubiquitin ligase complex plays an essential role in neurodevelopment by regulating synapse formation and growth. Since mounting evidence has established autism as a disorder of the synapses, we tested whether rare genetic variants in TSC1, TSC2, MYCBP2, RHEB and FBXO45, genes that regulate mTORC1 signaling and/or play a role in synapse development and function, contribute to the pathogenesis of idiopathic ASD. METHODS: Exons and splice junctions of TSC1, TSC2, MYCBP2, RHEB and FBXO45 were resequenced for 300 ASD trios from the Simons Simplex Collection (SSC) using a pooled PCR amplification and next-generation sequencing strategy, targeted to the discovery of deleterious coding variation. These detected, potentially functional, variants were confirmed by Sanger sequencing of the individual samples comprising the pools in which they were identified. RESULTS: We identified a total of 23 missense variants in MYCBP2, TSC1 and TSC2. These variants exhibited a near equal distribution between the proband and parental pools, with no statistical excess in ASD cases (P > 0.05). All proband variants were inherited. No putative deleterious variants were confirmed in RHEB and FBXO45. Three intronic variants, identified as potential splice defects in MYCBP2 did not show aberrant splicing upon RNA assay. Overall, we did not find an over-representation of ASD causal variants in the genes studied to support them as contributors to autism susceptibility. CONCLUSIONS: We did not observe an enrichment of rare functional variants in TSC1 and TSC2 genes in our sample set of 300 trios.
Lien vers le texte intégral (Open Access ou abonnement)
4. Clery H, Roux S, Houy-Durand E, Bonnet-Brilhault F, Bruneau N, Gomot M. {{Electrophysiological evidence of atypical visual change detection in adults with autism}}. {Front Hum Neurosci};2013;7:62.
Although atypical change detection processes have been highlighted in the auditory modality in autism spectrum disorder (ASD), little is known about these processes in the visual modality. The aim of the present study was therefore to investigate visual change detection in adults with ASD, taking into account the salience of change, in order to determine whether this ability is affected in this disorder. Thirteen adults with ASD and 13 controls were presented with a passive visual three stimuli oddball paradigm. The findings revealed atypical visual change processing in ASD. Whereas controls displayed a vMMN in response to deviant and a novelty P3 in response to novel stimuli, patients with ASD displayed a novelty P3 in response to both deviant and novel stimuli. These results thus suggested atypical orientation of attention toward unattended minor changes in ASD that might contribute to the intolerance of change.
Lien vers le texte intégral (Open Access ou abonnement)
5. Cobigo V, Ouellette-Kuntz H, Balogh R, Leung F, Lin E, Lunsky Y. {{Are cervical and breast cancer screening programmes equitable? The case of women with intellectual and developmental disabilities}}. {J Intellect Disabil Res};2013 (Mar 19)
BACKGROUND: Effective cancer screening must be available for all eligible individuals without discrimination. Lower rates of cervical and breast cancer screening have been reported in certain groups compared with women from the general population, such as women with intellectual and developmental disabilities (IDD). Research on the factors explaining those observed differences is crucial to determine whether practices are unfair and could be improved. The aim of this population-based study was to describe cancer screening utilisation by women with IDD in Ontario, Canada compared with other women in Ontario. The specific objectives were (1) to estimate the rates of cervical and breast cancer screening among eligible women with IDD in Ontario; (2) to compare the rates of cervical and breast cancer screening between eligible women with and without IDD; and (3) to examine if any observed differences between women with and without IDD persist after factors such as age, socio-economic status, rurality and healthcare utilisation are accounted for. METHOD: This study draws women with IDD from an entire population, and draws a randomly selected comparison group from the same population. It controls for important confounders in cancer screening within the limitations of the data sources. The study was conducted using health administrative databases and registries in Ontario, Canada. Two cohorts were created: a cohort of all women identified as having an IDD and a cohort consisting of a random sample of 20% of the women without IDD. RESULTS: The proportion of women with IDD who are not screened for cervical cancer is nearly twice what it is in the women without IDD, and 1.5 times what it is for mammography. CONCLUSIONS: Findings suggest that women with IDD experience inequities in their access to cancer screening. Public health interventions targeting this population should be implemented.
Lien vers le texte intégral (Open Access ou abonnement)
6. Dolan BM, Duron SG, Campbell DA, Vollrath B, Rao BS, Ko HY, Lin GG, Govindarajan A, Choi SY, Tonegawa S. {{Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486}}. {Proc Natl Acad Sci U S A};2013 (Mar 18)
Fragile X syndrome (FXS) is the most common inherited form of autism and intellectual disability and is caused by the silencing of a single gene, fragile X mental retardation 1 (Fmr1). The Fmr1 KO mouse displays phenotypes similar to symptoms in the human condition-including hyperactivity, repetitive behaviors, and seizures-as well as analogous abnormalities in the density of dendritic spines. Here we take a hypothesis-driven, mechanism-based approach to the search for an effective therapy for FXS. We hypothesize that a treatment that rescues the dendritic spine defect in Fmr1 KO mice may also ameliorate autism-like behavioral symptoms. Thus, we targeted a protein that regulates spines through modulation of actin cytoskeleton dynamics: p21-activated kinase (PAK). Our results demonstrate that a potent small molecule inhibitor of group I PAKs reverses dendritic spine phenotypes in Fmr1 KO mice. Moreover, this PAK inhibitor-which we call FRAX486-also rescues seizures and behavioral abnormalities such as hyperactivity and repetitive movements, thereby supporting the hypothesis that a drug treatment that reverses the spine abnormalities can also treat neurological and behavioral symptoms. Finally, a single administration of FRAX486 is sufficient to rescue all of these phenotypes in adult Fmr1 KO mice, demonstrating the potential for rapid, postdiagnostic therapy in adults with FXS.
Lien vers le texte intégral (Open Access ou abonnement)
7. Elison JT, Paterson SJ, Wolff JJ, Reznick JS, Sasson NJ, Gu H, Botteron KN, Dager SR, Estes AM, Evans AC, Gerig G, Hazlett HC, Schultz RT, Styner M, Zwaigenbaum L, Piven J. {{White Matter Microstructure and Atypical Visual Orienting in 7-Month-Olds at Risk for Autism}}. {Am J Psychiatry};2013 (Mar 20)
OBJECTIVE The authors sought to determine whether specific patterns of oculomotor functioning and visual orienting characterize 7-month-old infants who later meet criteria for an autism spectrum disorder (ASD) and to identify the neural correlates of these behaviors. METHOD Data were collected from 97 infants, of whom 16 were high-familial-risk infants later classified as having an ASD, 40 were high-familial-risk infants who did not later meet ASD criteria (high-risk negative), and 41 were low-risk infants. All infants underwent an eye-tracking task at a mean age of 7 months and a clinical assessment at a mean age of 25 months. Diffusion-weighted imaging data were acquired for 84 of the infants at 7 months. Primary outcome measures included average saccadic reaction time in a visually guided saccade procedure and radial diffusivity (an index of white matter organization) in fiber tracts that included corticospinal pathways and the splenium and genu of the corpus callosum. RESULTS Visual orienting latencies were longer in 7-month-old infants who expressed ASD symptoms at 25 months compared with both high-risk negative infants and low-risk infants. Visual orienting latencies were uniquely associated with the microstructural organization of the splenium of the corpus callosum in low-risk infants, but this association was not apparent in infants later classified as having an ASD. CONCLUSIONS Flexibly and efficiently orienting to salient information in the environment is critical for subsequent cognitive and social-cognitive development. Atypical visual orienting may represent an early prodromal feature of an ASD, and abnormal functional specialization of posterior cortical circuits directly informs a novel model of ASD pathogenesis.
Lien vers le texte intégral (Open Access ou abonnement)
8. Hrdlicka M, Dudova I. {{Controversies in autism: is a broader model of social disorders needed?}}. {Child Adolesc Psychiatry Ment Health};2013 (Mar 18);7(1):9.
This article examines the most significant, contradictory evidence pertaining to autism. The first section of the article includes reports of recovery from autism, data obtained from studies involving oxytocin, early deprivation, autism in preterm children, late-onset autism, and symptom overlap among ASD, social phobias and personality disorders. In the second section of the article, we offer a model that better incorporates current findings and address controversies that continue to surround ASD. We propose an umbrella term « social inhibition disorders » which integrates autism spectrum disorders and social phobias, as well as schizoid, schizotypal, and obsessive-compulsive personality disorders. It would also include « quasi-autism, » which has been found in early deprivation studies, autism in preterm children, and cases of late-onset autism presenting after herpes encephalitis infection. Finally, we discuss suggestions for further research and clinical perspectives.
Lien vers le texte intégral (Open Access ou abonnement)
9. McGrath J, Johnson K, O’Hanlon E, Garavan H, Gallagher L, Leemans A. {{White Matter and Visuospatial Processing in Autism: A Constrained Spherical Deconvolution Tractography Study}}. {Autism Res};2013 (Mar 18)
Autism spectrum disorders (ASDs) are associated with a marked disturbance of neural functional connectivity, which may arise from disrupted organization of white matter. The aim of this study was to use constrained spherical deconvolution (CSD)-based tractography to isolate and characterize major intrahemispheric white matter tracts that are important in visuospatial processing. CSD-based tractography avoids a number of critical confounds that are associated with diffusion tensor tractography, and to our knowledge, this is the first time that this advanced diffusion tractography method has been used in autism research. Twenty-five participants with ASD and aged 25, intelligence quotient-matched controls completed a high angular resolution diffusion imaging scan. The inferior fronto-occipital fasciculus (IFOF) and arcuate fasciculus were isolated using CSD-based tractography. Quantitative diffusion measures of white matter microstructural organization were compared between groups and associated with visuospatial processing performance. Significant alteration of white matter organization was present in the right IFOF in individuals with ASD. In addition, poorer visuospatial processing was associated in individuals with ASD with disrupted white matter in the right IFOF. Using a novel, advanced tractography method to isolate major intrahemispheric white matter tracts in autism, this research has demonstrated that there are significant alterations in the microstructural organization of white matter in the right IFOF in ASD. This alteration was associated with poorer visuospatial processing performance in the ASD group. This study provides an insight into structural brain abnormalities that may influence atypical visuospatial processing in autism. Autism Res 2013, : -. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
10. Piryaei F, Houshmand M, Aryani O, Dadgar S, Soheili ZS. {{Investigation of the Mitochondrial ATPase 6/8 and tRNA(Lys) Genes Mutations in Autism}}. {Cell J};2012 (Summer);14(2):98-101.
OBJECTIVE: Autism results from developmental factors that affect many or all functional brain systems. Brain is one of tissues which are crucially in need of adenosine triphosphate (ATP). Autism is noticeably affected by mitochondrial dysfunction which impairs energy metabolism. Considering mutations within ATPase 6, ATPase 8 and tRNA(Lys) genes, associated with different neural diseases, and the main role of ATPase 6/8 in energy generation, we decided to investigate mutations on these mtDNA-encoded genes to reveal their roles in autism pathogenesis. MATERIALS AND METHODS: In this experimental study, mutation analysis for the mentioned genes were performed in a cohort of 24 unrelated patients with idiopathic autism by employing amplicon sequencing of mtDNA fragments. RESULTS: In this study, 12 patients (50%) showed point mutations that represent a significant correlation between autism and mtDNA variations. Most of the identified substitutions (55.55%) were observed on MT-ATP6, altering some conserved amino acids to other ones which could potentially affect ATPase 6 function. Mutations causing amino acid replacement denote involvement of mtDNA genes, especially ATPase 6 in autism pathogenesis. CONCLUSION: MtDNA mutations in relation with autism could be remarkable to realize an understandable mechanism of pathogenesis in order to achieve therapeutic solutions.
11. Schwede M, Garbett K, Mirnics K, Geschwind DH, Morrow EM. {{Genes for endosomal NHE6 and NHE9 are misregulated in autism brains}}. {Mol Psychiatry};2013 (Mar 19)
