1. {{Autism DNA hub opens}}. {Nat Biotechnol}. 2016; 34(4): 364.
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2. Crawford H, Moss J, Oliver C, Elliott N, Anderson GM, McCleery JP. {{Visual preference for social stimuli in individuals with autism or neurodevelopmental disorders: an eye-tracking study}}. {Mol Autism}. 2016; 7: 24.
BACKGROUND: Recent research has identified differences in relative attention to competing social versus non-social video stimuli in individuals with autism spectrum disorder (ASD). Whether attentional allocation is influenced by the potential threat of stimuli has yet to be investigated. This is manipulated in the current study by the extent to which the stimuli are moving towards or moving past the viewer. Furthermore, little is known about whether such differences exist across other neurodevelopmental disorders. This study aims to determine if adolescents with ASD demonstrate differences in attentional allocation to competing pairs of social and non-social video stimuli, where the actor or object either moves towards or moves past the viewer, in comparison to individuals without ASD, and to determine if individuals with three genetic syndromes associated with differing social phenotypes demonstrate differences in attentional allocation to the same stimuli. METHODS: In study 1, adolescents with ASD and control participants were presented with social and non-social video stimuli in two formats (moving towards or moving past the viewer) whilst their eye movements were recorded. This paradigm was then employed with groups of individuals with fragile X, Cornelia de Lange, and Rubinstein-Taybi syndromes who were matched with one another on chronological age, global adaptive behaviour, and verbal adaptive behaviour (study 2). RESULTS: Adolescents with ASD demonstrated reduced looking-time to social versus non-social videos only when stimuli were moving towards them. Individuals in the three genetic syndrome groups showed similar looking-time but differences in fixation latency for social stimuli moving towards them. Across both studies, we observed within- and between-group differences in attention to social stimuli that were moving towards versus moving past the viewer. CONCLUSIONS: Taken together, these results provide strong evidence to suggest differential visual attention to competing social versus non-social video stimuli in populations with clinically relevant, genetically mediated differences in socio-behavioural phenotypes.
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3. Ishizuka K, Kimura H, Wang C, Xing J, Kushima I, Arioka Y, Oya-Ito T, Uno Y, Okada T, Mori D, Aleksic B, Ozaki N. {{Investigation of Rare Single-Nucleotide PCDH15 Variants in Schizophrenia and Autism Spectrum Disorders}}. {PLoS One}. 2016; 11(4): e0153224.
Both schizophrenia (SCZ) and autism spectrum disorders (ASD) are neuropsychiatric disorders with overlapping genetic etiology. Protocadherin 15 (PCDH15), which encodes a member of the cadherin super family that contributes to neural development and function, has been cited as a risk gene for neuropsychiatric disorders. Recently, rare variants of large effect have been paid attention to understand the etiopathology of these complex disorders. Thus, we evaluated the impacts of rare, single-nucleotide variants (SNVs) in PCDH15 on SCZ or ASD. First, we conducted coding exon-targeted resequencing of PCDH15 with next-generation sequencing technology in 562 Japanese patients (370 SCZ and 192 ASD) and detected 16 heterozygous SNVs. We then performed association analyses on 2,096 cases (1,714 SCZ and 382 ASD) and 1,917 controls with six novel variants of these 16 SNVs. Of these six variants, four (p.R219K, p.T281A, p.D642N, c.3010-1G>C) were ultra-rare variants (minor allele frequency < 0.0005) that may increase disease susceptibility. Finally, no statistically significant association between any of these rare, heterozygous PCDH15 point variants and SCZ or ASD was found. Our results suggest that a larger sample size of resequencing subjects is necessary to detect associations between rare PCDH15 variants and neuropsychiatric disorders. Lien vers le texte intégral (Open Access ou abonnement)
4. Mintz M. {{Evolution in the Understanding of Autism Spectrum Disorder: Historical Perspective}}. {Indian J Pediatr}. 2016.
The study of the evolution in the diagnosis and treatment of autism is a lesson in the dangers of medical beliefs or doctrines that are not grounded in medical science. The early descriptions of autism suggested that it was the result of childhood psychoses or psychodynamic disturbances of parent-child relationships. This flawed conceptualization of autism spectrum disorders (ASD) gave way to advances in medical science, which have established ASD as a neurobiological disorder of early brain development. There are many genetic, epigenetic, metabolic, hormonal, immunological, neuroanatomical and neurophysiological etiologies of ASD, as well as an array of gastrointestinal and other systemic co-morbid disorders. Thus, ASD are a biologically heterogeneous population with extensive neurodiversity. Early identification and understanding of ASD is crucial; interventions at younger ages are associated with improved outcomes. The advent of understanding the biological sub-phenotypes of ASD, along with targeted medical therapies, coupled with a multimodal therapeutic approach that encompasses behavioral, educational, social, speech, occupational, creative arts, and other forms of therapies has created a new and exciting era for individuals with ASD and their families: « personalized » and « precision » medical care based upon underlying biological sub-phenotypes and clinical profiles. For many individuals and their families dealing with the scourge of autism, their long and frustrating diagnostic journey is beginning to come to an end, with a hope for improved outcomes and quality of life.
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5. Mulhern T, Lydon S, Healy O, Mollaghan G, Ramey D, Leoni M. {{A systematic review and evaluation of procedures for the induction of speech among persons with developmental disabilities}}. {Dev Neurorehabil}. 2016: 1-21.
OBJECTIVE: Deficits in vocal speech are common among those with developmental disabilities. This review examines interventions for teaching speech to individuals who presented as nonspeaking, or with low levels of vocalizations at baseline, and assesses evidence-based practice in this area. METHODS: Systematic searches identified 78 studies suitable for inclusion. These studies were evaluated in terms of (a) participants, (b) intervention, (c) intervention setting, (d) intervention agent, (e) treatment efficacy, (f) generalization and maintenance of treatment effects, and (g) research rigor. RESULTS: A variety of interventions, primarily behavioral, intended to induce vocal speech were delivered to participants with developmental disabilities aged between six months and 57 years. Treatment efficacy was variable (PND M = 52.9%; range 0%-100%); however, results indicated that behavioral interventions constituted evidence-based practice. Non-behavioral strategies were shown to have received insufficient research evaluation to date. CONCLUSION: Results indicate that a number of procedures can induce speech among individuals with developmental disabilities.
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6. Pellerin D, Caku A, Fradet M, Bouvier P, Dube J, Corbin F. {{Lovastatin corrects ERK pathway hyperactivation in fragile X syndrome: potential of platelet’s signaling cascades as new outcome measures in clinical trials}}. {Biomarkers}. 2016: 1-12.
AIM: To establish whether platelets from fragile X syndrome (FXS) individuals recapitulate FXS mouse neurons’ defects in ERK and Akt pathways, and to evaluate the effect of lovastatin on these pathways. METHODS: ERK and Akt phosphorylation (pERK, pAkt) statuses were assessed with quantitative Western blotting before and after a 12-week lovastatin trial. RESULTS: Levels of pERK and pAkt were increased in FXS platelets, and lovastatin specifically normalized ERK activity. Changes in ERK phosphorylation were correlated with clinical response to lovastatin. CONCLUSIONS: Platelets’ signaling pathways provide biomarkers that can be used as treatment outcome measures in FXS clinical trials.
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7. Stasolla F, Perilli V, Damiani R, Albano V. {{Assistive technology to promote occupation and reduce mouthing by three boys with fragile X syndrome}}. {Dev Neurorehabil}. 2016: 1-9.
OBJECTIVES: To extend the use of assistive technology (AT) for promoting a new adaptive response and to reduce hand mouthing, by three boys with fragile X syndrome. To monitor the effects of the intervention program on the positive mood. To carry out a three month follow-up phases. To conduct a social validation assessment involving 30 parents of children who presented multiple disabilities as raters. METHODS: The study was implemented according to an ABAB experimental design, where A represented baseline phases (technology available but inactive) and B represented intervention phases (the technology ensured 7 s of positive stimulation). RESULTS: All participants improved and consolidated their performance. Parents involved in the social validation assessment rated positively the use of such technology. CONCLUSION: AT-based program was useful, affordable, and effective for enhancing constructive engagement, self-determination, and for improving quality of life by children with fragile X syndrome and severe to profound developmental disabilities.
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8. Steenweg-de Graaff J, Tiemeier H, Ghassabian A, Rijlaarsdam J, Jaddoe VW, Verhulst FC, Roza SJ. {{Maternal Fatty Acid Status During Pregnancy and Child Autistic Traits The Generation R Study}}. {Am J Epidemiol}. 2016.
omega-3 and omega-6 polyunsaturated fatty acids are important for brain function and development. We examined whether maternal polyunsaturated fatty acid status during pregnancy affects risk of autistic traits in childhood. Within the Generation R cohort, we measured maternal plasma polyunsaturated fatty acid concentrations and the omega-3:omega-6 ratio in midpregnancy (Rotterdam, the Netherlands, 2001-2005). Child autistic traits at 6 years were assessed by using the Social Responsiveness Scale short form in 4,624 children. A lower maternal omega-3:omega-6 ratio during pregnancy was associated with more autistic traits in the offspring (beta = -0.008, 95% confidence interval: -0.016, -0.001). In particular, a higher total omega-6 and linoleic acid status were associated with more autistic traits (allP’s < 0.05). Associations were independent of child intelligence, suggesting that the fatty acid distribution specifically affects the development of autistic traits in addition to general neurodevelopment. Maternal plasma omega-3 status was not associated with child autistic traits and, consistently, neither was prenatal dietary fish intake. Our study shows that a lower prenatal omega-3:omega-6 ratio is associated with more child autistic traits, which is largely accounted for by higher omega-6 instead of lower omega-3 status. These results suggest a biological pathway between maternal fatty acid intake during pregnancy and autistic traits in the offspring. Lien vers le texte intégral (Open Access ou abonnement)
9. Van Dijck A, Helsmoortel C, Vandeweyer G, Kooy F. {{ADNP-Related Intellectual Disability and Autism Spectrum Disorder}}. 1993.
ADNP-related intellectual disability and autism spectrum disorders (ADNP-related ID/ASD) are characterized by mild to severe intellectual disability and autism spectrum disorder (ASD). Of the 24 individuals reported to date, 23 were ascertained in cohorts with autism spectrum disorder (ASD) / intellectual disability (ID); one was identified in a clinical setting. The clinical information available on 12 of the 24 revealed: delayed developmental milestones (walking independently between 19 months and 4.5 years) and speech ranging from no words to sentences. ASD was characterized by stereotypic behavior and impaired social interaction. Other common findings include behavioral problems, sleep disturbance, hypotonia, seizures, feeding difficulties, visual problems (hypermetropia, strabismus, cortical visual impairment), and cardiac defects. The diagnosis of ADNP-related ID/ASD is established by identification of a heterozygous ADNP pathogenic variant on molecular genetic testing. Treatment of manifestations: Treatment is symptomatic and can include: speech, occupational, and physical therapy; specialized learning programs depending on individual needs; treatment of neuropsychiatric features (e.g., sleep disorders, behavioral problems, and/or seizures); nutritional support as needed; routine treatment of ophthalmologic and cardiac findings. ADNP-related ID/ASD is expressed in an autosomal dominant manner. Given that all affected individuals with ADNP-related syndromic autism reported to date have the disorder as a result of a de novo ADNP pathogenic variant, the risk to other family members is presumed to be low. Prenatal testing and preimplantation genetic diagnosis are possible options.
10. Wen Y, Alshikho MJ, Herbert MR. {{Pathway Network Analyses for Autism Reveal Multisystem Involvement, Major Overlaps with Other Diseases and Convergence upon MAPK and Calcium Signaling}}. {PLoS One}. 2016; 11(4): e0153329.
We used established databases in standard ways to systematically characterize gene ontologies, pathways and functional linkages in the large set of genes now associated with autism spectrum disorders (ASDs). These conditions are particularly challenging-they lack clear pathognomonic biological markers, they involve great heterogeneity across multiple levels (genes, systemic biological and brain characteristics, and nuances of behavioral manifestations)-and yet everyone with this diagnosis meets the same defining behavioral criteria. Using the human gene list from Simons Foundation Autism Research Initiative (SFARI) we performed gene set enrichment analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database, and then derived a pathway network from pathway-pathway functional interactions again in reference to KEGG. Through identifying the GO (Gene Ontology) groups in which SFARI genes were enriched, mapping the coherence between pathways and GO groups, and ranking the relative strengths of representation of pathway network components, we 1) identified 10 disease-associated and 30 function-associated pathways 2) revealed calcium signaling pathway and neuroactive ligand-receptor interaction as the most enriched, statistically significant pathways from the enrichment analysis, 3) showed calcium signaling pathways and MAPK signaling pathway to be interactive hubs with other pathways and also to be involved with pervasively present biological processes, 4) found convergent indications that the process « calcium-PRC (protein kinase C)-Ras-Raf-MAPK/ERK » is likely a major contributor to ASD pathophysiology, and 5) noted that perturbations associated with KEGG’s category of environmental information processing were common. These findings support the idea that ASD-associated genes may contribute not only to core features of ASD themselves but also to vulnerability to other chronic and systemic problems potentially including cancer, metabolic conditions and heart diseases. ASDs may thus arise, or emerge, from underlying vulnerabilities related to pleiotropic genes associated with pervasively important molecular mechanisms, vulnerability to environmental input and multiple systemic co-morbidities.
