1. Abbeduto L, Berry-Kravis E, Sterling A, Sherman S, Edgin JO, McDuffie A, Hoffmann A, Hamilton D, Nelson M, Aschkenasy J, Thurman AJ. {{Correction to: Expressive language sampling as a source of outcome measures for treatment studies in fragile X syndrome: feasibility, practice effects, test-retest reliability, and construct validity}}. {J Neurodev Disord}. 2020; 12(1): 11.
In the original publication of this article [1], the author name Leonard Abbeduto was misspelled as Leonardkk Abbeduto. The original article has been corrected.
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2. Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Al-Ayadhi LY, Alasmari AF, Alanazi MM, Al-Mazroua HA, Attia SM. {{Involvement of CD45 cells in the development of autism spectrum disorder through dysregulation of granulocyte-macrophage colony-stimulating factor, key inflammatory cytokines, and transcription factors}}. {International immunopharmacology}. 2020; 83: 106466.
Autismspectrum disorder (ASD) is a complex and multifactorial heterogeneous disorder. Previous investigations have revealed the association between the immune system and ASD, which is characterized by impaired communication skills. Inflammatory response through CD45 cells plays a key role in the pathogenesis of several autoimmune disorders; however, the molecular mechanism of CD45 cells in ASD is not clearly defined.In this study, we investigated the role of CD45 signaling in children with ASD. In this study, we aimed to investigate the possible involvement of CD45 cells expressing granulocyte-macrophage colony-stimulating factor and inflammatory transcription factors in ASD. Flow cytometric analysis, using peripheral blood mononuclear cells (PBMC), revealed the numbers of GM-CSF-, IFN-gamma-, IL-6-, IL-9-, IL-22-, T-bet-, pStat3-, Helios-, and Stat6-producing CD45(+) cells in children with ASD and children in the control group. We further evaluated the mRNA and protein expression levels of GM-CSF in PBMC by RT-PCR and western blotting analysis. Our results revealed that the children with ASD exhibited significantly higher numbers of CD45(+)GM-CSF(+), CD45(+)IFN-gamma(+), CD45(+)IL-6(+), CD45(+)IL-9(+), CD45(+)IL-22(+), CD45(+)T-bet(+), and CD45(+)pStat3(+) cells compared with the control group. We also found that the children with ASD showed a lower number of CD45(+)Helios(+) and CD45(+)Stat6(+) cells compared with the control group. Furthermore, the children with ASD showed higher GM-CSF mRNA and protein expression levels compared with the control group. These results indicated that CD45 could play an essential role in the immune abnormalities of ASD. Further investigation of the role of CD45 in neurodevelopment in ASD is warranted.
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3. Coffman MC, Shaffer RC, Schmitt LM, Dominick KC, Pedapati E, Wang A, Berry-Kravis E, Tartaglia N, Erickson CA. {{Examination of Correlates to Health-Related Quality of Life in Individuals with Fragile X Syndrome}}. {Brain Sci}. 2020; 10(4).
Health-related quality of life (HRQoL) is a multidimensional concept involving physical, psychological, social, and cognitive aspects of life. Individuals with Fragile X syndrome (FXS) experience a life-long disorder that impacts the HRQoL of the affected individual and their family. Thus, HRQoL may be an important outcome measure following intervention. However, it is yet not known whether HRQoL concerns relate to observed impairments in FXS. In the present study, we examined the nature and degree of association between HRQoL and established measures of functioning in FXS using the Parent Report for Children version of the PedsQL 4.0 Generic Core Scales and Cognitive Functioning Scale. We observed significant relationships between HRQoL a nd measures of adaptive behavior, maladaptive behaviors, and social functioning. The present study has implications for treatment outcomes for clinical trials in FXS.
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4. Hartley C, Bird LA, Monaghan P. {{Comparing cross-situational word learning, retention, and generalisation in children with autism and typical development}}. {Cognition}. 2020; 200: 104265.
Word learning is complicated by referential ambiguity – there are often multiple potential targets for a newly-heard word. While typically developing (TD) children can accurately infer word meanings from cross-situational statistics, specific difficulties tracking word-object co-occurrences may contribute to language impairments in autism spectrum disorder (ASD). Here, we investigate cross-situational word learning as an integrated system including mapping, retention, and generalisation in both typical development and autism. In Study 1, children with ASD were as accurate at disambiguating the meanings of novel words from statistical correspondences as TD controls matched on receptive vocabulary. In Study 2, both populations spontaneously utilised social and non-social attentional cues to facilitate and accelerate their mapping of word-referent relationships. Across Studies 1 and 2, both groups retrieved and generalised word-referent representations with impressive and comparable accuracy. Although children with ASD performed very similarly to TD children on measures of learning accuracy, they were significantly slower to identify correct referents under both cued and non-cued learning conditions. These findings indicate that mechanisms supporting cross-situational word learning, and the relationships between them, are not qualitatively atypical in language-delayed children with ASD. However, the increased time required to generate correct responses suggests that these mechanisms may be less efficient, potentially impacting learning in natural environments where visual and auditory stimuli are presented rapidly. Our data support claims that word learning in the longer term is driven by the gradual accumulation of word-object associations over multiple learning instances and could potentially inform the development of interventions designed to scaffold word learning.
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5. Hoffmann A, Wang A, Berger N, Cordeiro L, Shaffer R, Tartaglia N, Erickson C, Berry-Kravis E. {{Language across the Lifespan in Fragile X Syndrome: Characteristics and Considerations for Assessment}}. {Brain Sci}. 2020; 10(4).
While it is widely acknowledged that language development is delayed for the majority of individuals with fragile X syndrome (FXS), there has been limited research into how best to assess this area. This study aimed to deepen the understanding of standardized language assessment in FXS by addressing the three following objectives: (1) Examine the feasibility and validity of widely-used, standardized assessments in participants with FXS; (2) describe linguistic and cognitive profiles for a large sample of individuals with FXS; and (3) Compare results obtained from objective testing in clinic to those obtained using caregiver report. Results indicate that previous results indicating strong correlations between cognition and language results hold true across a wide range of ages as well as across multiple assessments, with an exception in very young children. Caregiver report tended to give lower estimates of language ability than what was found using an objectively administered assessment. Appropriate assessments remain difficult to find as a significant percentage of individuals scored at floor when scaled scores were calculated. Further, a sub-group of participants were coded for behavioral response to testing demands, the majority being able to complete a standardized assessment. These results speak to the need for assessments that provide a wider range of items so individuals can both achieve a valid score and demonstrate progress in their attainment of language skills.
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6. Kerr-Gaffney J, Harrison A, Tchanturia K. {{The social responsiveness scale is an efficient screening tool for autism spectrum disorder traits in adults with anorexia nervosa}}. {European eating disorders review : the journal of the Eating Disorders Association}. 2020.
OBJECTIVE: A significant proportion of individuals with anorexia nervosa (AN) show high levels of autism spectrum disorder (ASD) traits, a factor associated with poorer treatment outcomes. An important question for both researchers and clinicians relates to how ASD traits should be assessed in individuals with AN. This study aimed to examine scores on the Social Responsiveness Scale adult self-report version (SRS-2) in individuals in the acute (AN) and recovered stages (REC) of illness compared to healthy controls (HCs). We also aimed to examine associations between the SRS-2 and an observational diagnostic measure, the Autism Diagnostic Observation Schedule – second edition (ADOS-2). METHOD: The SRS-2 and ADOS-2 were administered to 142 adults with AN, REC, and HCs. Eating disorder (ED) psychopathology and functional impairment were also assessed. RESULTS: AN and REC scored significantly higher than HCs on the SRS-2. SRS-2 scores significantly predicted ADOS-2 classification and were positively associated with ED psychopathology and functional impairment. SRS-2 scores were not associated with BMI or illness duration. CONCLUSIONS: The SRS-2 may be a useful tool in screening for ASD traits in individuals with AN. Although cross-sectional, the results also suggest ASD symptoms are independent of BMI and persist in individuals recovered from AN.
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7. Koegel LK, Bryan KM, Su PL, Vaidya M, Camarata S. {{Parent Education in Studies With Nonverbal and Minimally Verbal Participants With Autism Spectrum Disorder: A Systematic Review}}. {American journal of speech-language pathology}. 2020: 1-13.
Purpose The purpose of this systematic review was to identify parent education procedures implemented in intervention studies focused on expressive verbal communication for nonverbal (NV) or minimally verbal (MV) children with autism spectrum disorder (ASD). Parent education has been shown to be an essential component in the habilitation of individuals with ASD. Parents of individuals with ASD who are NV or MV may particularly benefit from parent education in order to provide opportunities for communication and to support their children across the life span. Method ProQuest databases were searched between the years of 1960 and 2018 to identify articles that targeted verbal communication in MV and NV individuals with ASD. A total of 1,231 were evaluated to assess whether parent education was implemented. We found 36 studies that included a parent education component. These were reviewed with regard to (a) the number of participants and participants’ ages, (b) the parent education program provided, (c) the format of the parent education, (d) the duration of the parent education, (e) the measurement of parent education, and (f) the parent fidelity of implementation scores. Results The results of this analysis showed that very few studies have included a parent education component, descriptions of the parent education programs are unclear in most studies, and few studies have scored the parents’ implementation of the intervention. Conclusions Currently, there is great variability in parent education programs in regard to participant age, hours provided, fidelity of implementation, format of parent education, and type of treatment used. Suggestions are made to provide both a more comprehensive description and consistent measurement of parent education programs.
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8. Liu H, Zimmerman AW, Singh K, Connors SL, Diggins E, Stephenson KK, Dinkova-Kostova AT, Fahey JW. {{Biomarker Exploration in Human Peripheral Blood Mononuclear Cells for Monitoring Sulforaphane Treatment Responses in Autism Spectrum Disorder}}. {Sci Rep}. 2020; 10(1): 5822.
Autism Spectrum Disorder (ASD) is one of the most common neurodevelopmental disorders with no drugs treating the core symptoms and no validated biomarkers for clinical use. The multi-functional phytochemical sulforaphane affects many of the biochemical abnormalities associated with ASD. We investigated potential molecular markers from three ASD-associated physiological pathways that can be affected by sulforaphane: redox metabolism/oxidative stress; heat shock response; and immune dysregulation/inflammation, in peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with ASD. We first analyzed the mRNA levels of selected molecular markers in response to sulforaphane ex vivo treatment in PBMCs from healthy donors by real-time quantitative PCR. All of the tested markers showed quantifiability, accuracy and reproducibility. We then compared the expression levels of those markers in PBMCs taken from ASD patients in response to orally-delivered sulforaphane. The mRNA levels of cytoprotective enzymes (NQO1, HO-1, AKR1C1), and heat shock proteins (HSP27 and HSP70), increased. Conversely, mRNA levels of pro-inflammatory markers (IL-6, IL-1beta, COX-2 and TNF-alpha) decreased. Individually none is sufficiently specific or sensitive, but when grouped by function as two panels, these biomarkers show promise for monitoring pharmacodynamic responses to sulforaphane in both healthy and autistic humans, and providing guidance for biomedical interventions.
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9. Ludlow AK, Giannadou A, Franklin A, Allen PM, Simmons DR, Wilkins AJ. {{The possible use of precision tinted lenses to improve social cognition in children with autism spectrum disorders}}. {Vision research}. 2020; 170: 53-9.
A masked randomised control design compared the effectiveness of precision ophthalmic tints in improving the recognition of emotion in Autism Spectrum Disorders (ASD). Fourteen children aged 10-14 with ASD and 14 control children matched on verbal and non-verbal IQ, wore spectacles with coloured lenses to complete two tasks that involved the observation of coloured video sequences in which social interactions were depicted. On one occasion (randomly first or second) the coloured lenses provided light of a colour that the child had one month previously selected as optimal for the clarity of text. On the other occasion the lenses differed in CIE UCS chromaticity by 0.077. Performance in the ASD group was superior in both social interaction tasks with the lenses that provided the optimal colour of light.
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10. Ness S, Pandina G, Jagannatha S, Wathen K, Bangerter A, Manyakov NV, Hendren R, Leventhal B, Murphy D, Dawson G, Drevets WC, Manji HK. {{ASPI: a public-private partnership to develop treatments for autism}}. {Nature reviews Drug discovery}. 2020; 19(4): 219-20.
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11. Nguyen TA, Wu K, Pandey S, Lehr AW, Li Y, Bemben MA, Badger JD, 2nd, Lauzon JL, Wang T, Zaghloul KA, Thurm A, Jain M, Lu W, Roche KW. {{A Cluster of Autism-Associated Variants on X-Linked NLGN4X Functionally Resemble NLGN4Y}}. {Neuron}. 2020.
Autism spectrum disorder (ASD) is more prevalent in males; however, the etiology for this sex bias is not well understood. Many mutations on X-linked cell adhesion molecule NLGN4X result in ASD or intellectual disability. NLGN4X is part of an X-Y pair, with NLGN4Y sharing approximately 97% sequence homology. Using biochemistry, electrophysiology, and imaging, we show that NLGN4Y displays severe deficits in maturation, surface expression, and synaptogenesis regulated by one amino acid difference with NLGN4X. Furthermore, we identify a cluster of ASD-associated mutations surrounding the critical amino acid in NLGN4X, and these mutations phenocopy NLGN4Y. We show that NLGN4Y cannot compensate for the functional deficits observed in ASD-associated NLGN4X mutations. Altogether, our data reveal a potential pathogenic mechanism for male bias in NLGN4X-associated ASD.
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12. Pecorelli A, Ferrara F, Messano N, Cordone V, Schiavone ML, Cervellati F, Woodby B, Cervellati C, Hayek J, Valacchi G. {{Alterations of mitochondrial bioenergetics, dynamics, and morphology support the theory of oxidative damage involvement in autism spectrum disorder}}. {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}. 2020.
Autism spectrum disorder (ASD) has been hypothesized to be a result of the interplay between genetic predisposition and increased vulnerability to early environmental insults. Mitochondrial dysfunctions appear also involved in ASD pathophysiology, but the mechanisms by which such alterations develop are not completely understood. Here, we analyzed ASD primary fibroblasts by measuring mitochondrial bioenergetics, ultrastructural and dynamic parameters to investigate the hypothesis that defects in these pathways could be interconnected phenomena responsible or consequence for the redox imbalance observed in ASD. High levels of 4-hydroxynonenal protein adducts together with increased NADPH (nicotinamide adenine dinucleotide phosphateoxidase) activity and mitochondrial superoxide production coupled with a compromised antioxidant response guided by a defective Nuclear Factor Erythroid 2-Related Factor 2 pathway confirmed an unbalanced redox homeostasis in ASD. Moreover, ASD fibroblasts showed overactive mitochondrial bioenergetics associated with atypical morphology and altered expression of mitochondrial electron transport chain complexes and dynamics-regulating factors. We suggest that many of the changes observed in mitochondria could represent compensatory mechanisms by which ASD cells try to adapt to altered energy demand, possibly resulting from a chronic oxinflammatory status.
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13. Pejhan S, Mok Siu V, Ang LC, Del Bigio MR, Rastegar M. {{Differential brain region-specific expression of MeCP2 and BDNF in Rett Syndrome patients: A distinct grey-white matter variation}}. {Neuropathology and applied neurobiology}. 2020.
INTRODUCTION AND OBJECTIVES: Rett Syndrome (RTT) is a neurodevelopmental disorder caused by Methyl CpG Binding Protein 2 (MECP2) gene mutations. Previous studies of MeCP2 in the human brain showed variable and inconsistent mosaic-pattern immunolabelling, which has been interpreted as a reflection of activation-state variability. We aimed to study post-mortem MeCP2 and BDNF (MeCP2 target) degradation and brain region-specific detection in relation to RTT pathophysiology. METHODS: We investigated MeCP2 and BDNF stabilities in non-RTT human brains by immunohistochemical labelling and compared them in three brain regions of RTT and controls. RESULTS: In surgically excised samples of human hippocampus and cerebellum, MeCP2 was universally detected. There was no significantly obvious difference between males and females. However, post-mortem delay in autopsy samples had substantial influence on MeCP2 detection. Immunohistochemistry studies in RTT patients showed lower MeCP2 detection in glial cells of the white matter. Glial fibrillary acidic protein (GFAP) expression was also reduced in RTT brain samples without obvious change in myelin basic protein (MBP). Neurons did not show any noticeable decrease in MeCP2 detection. BDNF immunohistochemical detection showed an astroglial/endothelial pattern without noticeable difference between RTT and controls. CONCLUSIONS: Our findings indicate that MeCP2 protein is widely expressed in mature human brain cells at all ages. However, our data points towards a possible white matter abnormality in RTT and highlights the importance of studying human RTT brain tissues in parallel with research on animal and cell models of RTT.
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14. Slaughter AM, Hein S, Hong JH, Mire SS, Grigorenko EL. {{Correction to: Criminal Behavior and School Discipline in Juvenile Justice-Involved Youth with Autism}}. {J Autism Dev Disord}. 2020.
The original version of the article has unfortunately contained formatting errors in tables.
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15. Tajik-Parvinchi DJ, Farmus L, Cribbie R, Albaum C, Weiss JA. {{Clinical and parental predictors of emotion regulation following cognitive behaviour therapy in children with autism}}. {Autism}. 2020: 1362361320909178.
LAY ABSTRACT: Children with autism commonly experience difficulty controlling their emotions. Although existing treatments are successful in teaching critical emotion regulation skills, not all children improve. It is important to identify the factors that influence treatment response to be able to reach more children. This study aimed to identify child and parent characteristics that predict treatment response in a 10-week cognitive behaviour therapy treatment for children with autism, 8-12 years of age, and their parents. We found that youth who started the treatment with higher verbal abilities, who were more anxious in social situations, and had parents who were more anxious, were more likely to improve in learning new emotion regulation skills. We also found that children who had more physical discomforts or complaints before starting the treatment were less likely to improve in their negative expressions of emotion. Our study suggests that it is important for clinicians to promote active involvement and learning by avoiding complex language and to use more visual materials to supplement the learning process, and make sure that sessions are sensitive to the individual needs of participants.
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16. Tan DW, Foo YZ, Downs J, Finlay-Jones A, Leonard H, Licari MK, Mullan N, Symons M, Varcin KJ, Whitehouse AJO, Alvares GA. {{A preliminary investigation of the effects of prenatal alcohol exposure on facial morphology in children with Autism Spectrum Disorder}}. {Alcohol (Fayetteville, NY)}. 2020.
Alcohol exposure during pregnancy has been associated with altered brain development and facial dysmorphology. While autism spectrum disorder (ASD) is not specifically related to distinct facial phenotypes, recent studies have suggested certain facial characteristics such as increased facial masculinity and asymmetry may be associated with ASD and its clinical presentations. In the present study, we conducted a preliminary investigation to examine facial morphology in autistic children with (n = 37; mean age = 8.21 years, SD = 2.72) and without (n = 100; mean age = 8.37 years, SD = 2.47) prenatal alcohol exposure. Using three-dimensional facial scans and principal component analysis, we identified a facial shape associated with prenatal alcohol exposure in autistic children. However, variations in the alcohol-related facial shape were generally not associated with behavioural and cognitive outcomes. These findings suggest that while early exposure to alcohol may influence the development of facial structures, it does not appear to be associated with ASD phenotypic variability. Importantly, although these findings do not implicate a role for prenatal alcohol exposure in the etiology of ASD, further research is warranted to investigate the link between prenatal alcohol exposure and facial morphology differences among neurodevelopmental conditions.
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17. Turgeon S, Lanovaz MJ, Dufour MM. {{Effects of an Interactive Web Training to Support Parents in Reducing Challenging Behaviors in Children with Autism}}. {Behav Modif}. 2020: 145445520915671.
Many children with autism spectrum disorder (ASD) engage in challenging behaviors, which may interfere with their daily functioning, development, and well-being. To address this issue, we conducted a four-week randomized waitlist control trial to examine the effects of a fully self-guided interactive web training (IWT) on (a) child engagement in challenging behaviors and (b) parental intervention. After 4 weeks, parents in the treatment group reported lower levels of challenging behaviors in their children and more frequent use of behavioral interventions than those in the waitlist groups. Furthermore, within-group analyses suggest that these changes persisted up to 12 weeks following completion of the IWT. Our results highlight the potential utility of web training, but our high attrition rate and potential side effects prevent us from recommending the training as a standalone treatment.
