Pubmed du 29/06/20

lundi 29 juin 2020

1. Baisa A, Mevorach C, Shalev L. Hierarchical Processing in ASD is Driven by Exaggerated Salience Effects, not Local Bias. J Autism Dev Disord ;2020 (Jun 29)

The role of relative salience in processing of hierarchical stimuli in individuals with autism spectrum disorder (ASD) was examined in this study. Participants with ASD and typically developing controls performed a Navon letters task under conditions of global salience, local salience or equal salience of both levels. Results revealed no group differences in level of processing (global or local) and no local bias for ASD. Rather, both groups showed better performance when targets were more salient compared to when distractors were more salient. Importantly, participants with ASD exhibited increased sensitivity to salience at the distractor level. We conclude that inconsistent findings in the context of global/local processing in ASD may stem from such exaggerated salience effects.

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2. Bradshaw J, Trumbull A, Stapel-Wax J, Gillespie S, George N, Saulnier C, Klaiman C, Woods J, Call N, Klin A, Wetherby A. Factors associated with enrollment into a clinical trial of caregiver-implemented intervention for infants at risk for autism spectrum disorder. Autism ;2020 (Jun 29):1362361320928829.

Early intervention helps to address developmental delays in young children with autism spectrum disorder. Yet, research suggests there are barriers to enrollment into research studies that test the effectiveness of these interventions for infants at risk. This study identifies family characteristics that were associated with agreement to enroll in a clinical trial of early intervention for 12-month-old infants at risk for autism spectrum disorder. As part of a large longitudinal study, infants were evaluated for early signs of autism spectrum disorder at 1 year of age. Of the fifty-seven infants who were showing signs of autism and deemed eligible for the early intervention trial, 44% declined enrollment. Results suggest that families were more likely to decline enrolling into the intervention study if the mother was working full time, the total household income was between US$60,000 and US$100,000, and they lived further from the clinic. In contrast, infant autism symptoms and parental concern at 12 months were not significantly associated with enrollment. These findings highlight the need for intervention studies that are more accessible to parents, for example, intervention that takes place in the home, in addition to more research on how parental understanding of, and willingness to act on, early social-communication delays impact intervention study enrollment. Future research can then examine how to address these barriers to enrollment in early intervention studies. Such findings will shed light on best practices for dissemination of early identification and intervention strategies.

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3. Carter Leno V, Bedford R, Chandler S, White P, Yorke I, Charman T, Pickles A, Simonoff E. Callous-unemotional traits in youth with autism spectrum disorder (ASD) : replication of prevalence estimates and associations with gaze patterns when viewing fearful faces. Dev Psychopathol ;2020 (Jun 29):1-9.

Research suggests an increased prevalence of callous-unemotional (CU) traits in children with autism spectrum disorder (ASD), and a similar impairment in fear recognition to that reported in non-ASD populations. However, past work has used measures not specifically designed to measure CU traits and has not examined whether decreased attention to the eyes reported in non-ASD populations is also present in individuals with ASD. The current paper uses a measure specifically designed to measure CU traits to estimate prevalence in a large community-based ASD sample. Parents of 189 adolescents with ASD completed questionnaires assessing CU traits, and emotional and behavioral problems. A subset of participants completed a novel emotion recognition task (n = 46). Accuracy, reaction time, total looking time, and number of fixations to the eyes and mouth were measured. Twenty-two percent of youth with ASD scored above a cut-off expected to identify the top 6% of CU scores. CU traits were associated with longer reaction times to identify fear and fewer fixations to the eyes relative to the mouth during the viewing of fearful faces. No associations were found with accuracy or total looking time. Results suggest the mechanisms that underpin CU traits may be similar between ASD and non-ASD populations.

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4. Chehbani F, Gallello G, Brahim T, Ouanes S, Douki W, Gaddour N, Cervera Sanz ML. The status of chemical elements in the blood plasma of children with autism spectrum disorder in Tunisia : a case-control study. Environ Sci Pollut Res Int ;2020 (Jun 29)

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders defined by a deficit in social interactions and the presence of restricted and stereotypical behaviors or interests. The etiologies of autism remain mostly unknown. Many genetic and environmental factors have been suspected. Among these environmental factors, exposure to several chemical elements has been previously studied. The purpose of this study was to compare the levels of trace elements in the blood plasma of children with ASD with typically developed children (TDC). The participants in this study consisted of 89 children with ASD (14 girls and 74 boys) and 70 TD children (29 girls and 41 boys). The levels of 33 chemical elements have been analyzed by inductively coupled plasma spectrometry (ICP-MS). We detected significant differences in the levels of eight elements between the two groups, among which there were three rare earth elements (REEs) : Eu, Pr, and Sc (p = 0.000, p = 0.023, and p < 0.001 respectively) ; four heavy metals : Bi, Tl, Ti, and V (p = 0.004, p < 0.001, p = 0.001, and p = 0.001 respectively) ; and one essential element : Cu (p = 0.043). Children with ASD had higher levels of Er, Pr, Sc, Bi, Tl, Ti, and V, and lower levels of Cu in comparison with the TD group. The children exposed to passive smoking had lower levels of lead (Pb) compared with children without exposure (p = 0.018). Four elements (Cr, Er, Dy, and Pr) were negatively correlated to the severity of ASD. The level of Cu was significantly associated with autistic children’s behavior (p = 0.014). These results suggest that children with ASD might have abnormal plasma levels of certain chemical elements (including Er, Pr, Sc, Bi, Tl, Ti, and V, and Cu), and some of these elements might be associated with certain clinical features.

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5. Garribba L, Bjerregaard VA, Gonçalves Dinis MM, Özer Ö, Wu W, Sakellariou D, Pena-Diaz J, Hickson ID, Liu Y. Folate stress induces SLX1- and RAD51-dependent mitotic DNA synthesis at the fragile X locus in human cells. Proc Natl Acad Sci U S A ;2020 (Jun 29)

Folate deprivation drives the instability of a group of rare fragile sites (RFSs) characterized by CGG trinucleotide repeat (TNR) sequences. Pathological expansion of the TNR within the FRAXA locus perturbs DNA replication and is the major causative factor for fragile X syndrome, a sex-linked disorder associated with cognitive impairment. Although folate-sensitive RFSs share many features with common fragile sites (CFSs ; which are found in all individuals), they are induced by different stresses and share no sequence similarity. It is known that a pathway (termed MiDAS) is employed to complete the replication of CFSs in early mitosis. This process requires RAD52 and is implicated in generating translocations and copy number changes at CFSs in cancers. However, it is unclear whether RFSs also utilize MiDAS and to what extent the fragility of CFSs and RFSs arises by shared or distinct mechanisms. Here, we demonstrate that MiDAS does occur at FRAXA following folate deprivation but proceeds via a pathway that shows some mechanistic differences from that at CFSs, being dependent on RAD51, SLX1, and POLD3. A failure to complete MiDAS at FRAXA leads to severe locus instability and missegregation in mitosis. We propose that break-induced DNA replication is required for the replication of FRAXA under folate stress and define a cellular function for human SLX1. These findings provide insights into how folate deprivation drives instability in the human genome.

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6. McMahon CM, Henry S, Linthicum M. Employability in autism spectrum disorder (ASD) : Job candidate’s diagnostic disclosure and asd characteristics and employer’s ASD knowledge and social desirability. J Exp Psychol Appl ;2020 (Jun 29)

Participants assessed the employability of vignette characters whose presentation varied across two dimensions during a job interview : presence of autism spectrum disorder (ASD) characteristics (present, absent) and disclosure of diagnosis (ASD, ADHD, diabetes, or no disclosure). Participants more knowledgeable about ASD had more positive perceptions of vignette characters, particularly when they disclosed an ASD diagnosis and did not show ASD characteristics. Participants high in social desirability perceived vignette characters more positively. Participants expressed the most concern about job candidates showing inflexible adherence to a routine and sensory sensitivity, although such concerns may have been context-dependent due to job expectations. Overall, these results emphasize that employer factors, particularly employer knowledge of ASD and social desirability, significantly affect the perceived employability of job candidates with ASD. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

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7. Paşca SP, Veenstra-VanderWeele J, McPartland JC. Research and training in autism spectrum disorder to catalyze the next genomic and neuroscience revolutions. Mol Psychiatry ;2020 (Jun 29)

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8. Perry A, Charles M, Zapparoli B, Weiss JA. School satisfaction in parents of children with severe developmental disabilities. J Appl Res Intellect Disabil ;2020 (Jun 29)

BACKGROUND : Previous research suggests parents’ level of satisfaction with their child’s school experience is highly variable. The present author explored school satisfaction in a Canadian sample of parents of children with severe and often complex developmental disabilities. METHOD : Parents of 185 children completed questionnaires regarding their satisfaction with nine aspects of their child’s school experience. Satisfaction was examined in relation to child’s age, diagnosis of Autism, adaptive level, and maladaptive behaviour ; parents’ mental health difficulties and perception of caring burden ; and the child’s classroom type and level of clinical services at school. RESULTS : School satisfaction was unrelated to parents’ mental health or burden scores, was related to child’s adaptive and maladaptive behaviour, as well as type of classroom placement. CONCLUSIONS : It is important to understand what aspects of the school experience are influential for different children and families so that their experience can be optimized as far as possible.

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9. Tsilioni I, Pantazopoulos H, Conti P, Leeman SE, Theoharides TC. IL-38 inhibits microglial inflammatory mediators and is decreased in amygdala of children with autism spectrum disorder. Proc Natl Acad Sci U S A ;2020 (Jun 29)

Autism spectrum disorder (ASD) is characterized by impaired social interactions and communication. The pathogenesis of ASD is not known, but it involves activation of microglia. We had shown that the peptide neurotensin (NT) is increased in the serum of children with ASD and stimulates cultured adult human microglia to secrete the proinflammatory molecules IL-1β and CXCL8. This process is inhibited by the cytokine IL-37. Another cytokine, IL-38, has been reported to have antiinflammatory actions. In this report, we show that pretreatment of cultured adult human microglia with recombinant IL-38 (aa3-152, 1-100 ng/mL) inhibits (P < 0.0001) NT-stimulated (10 nM) secretion of IL-1β (at 1 ng/mL) and CXCL8 (at 100 ng/mL). In fact, IL-38 (aa3-152, 1 ng/mL) is more potent than IL-37 (100 ng/mL). Here, we report that pretreatment with IL-38 (100 ng/mL) of embryonic microglia (HMC3), in which secretion of IL-1β was undetectable, inhibits secretion of CXCL8 (P = 0.004). Gene expression of IL-38 and its receptor IL-36R are decreased (P = 0.001 and P = 0.04, respectively) in amygdala from patients with ASD (n = 8) compared to non-ASD controls (n = 8), obtained from the University of Maryland NeuroBioBank. IL-38 is increased (P = 0.03) in the serum of children with ASD. These findings indicate an important role for IL-38 in the inhibition of activation of human microglia, thus supporting its development as a treatment approach for ASD.

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10. Yost RT, Robinson JW, Baxter CM, Scott AM, Brown LP, Aletta MS, Hakimjavadi R, Lone A, Cumming RC, Dukas R, Mozer B, Simon AF. Abnormal Social Interactions in a Drosophila Mutant of an Autism Candidate Gene : Neuroligin 3. Int J Mol Sci ;2020 (Jun 29) ;21(13)

Social interactions are typically impaired in neuropsychiatric disorders such as autism, for which the genetic underpinnings are very complex. Social interactions can be modeled by analysis of behaviors, including social spacing, sociability, and aggression, in simpler organisms such as Drosophila melanogaster. Here, we examined the effects of mutants of the autism-related gene neuroligin 3 (nlg3) on fly social and non-social behaviors. Startled-induced negative geotaxis is affected by a loss of function nlg3 mutation. Social space and aggression are also altered in a sex- and social-experience-specific manner in nlg3 mutant flies. In light of the conserved roles that neuroligins play in social behavior, our results offer insight into the regulation of social behavior in other organisms, including humans.

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