1. Courchet V, Roberts AJ, Meyer-Dilhet G, Del Carmine P, Lewis TL, Jr., Polleux F, Courchet J. {{Haploinsufficiency of autism spectrum disorder candidate gene NUAK1 impairs cortical development and behavior in mice}}. {Nature communications}. 2018; 9(1): 4289.
Recently, numerous rare de novo mutations have been identified in patients diagnosed with autism spectrum disorders (ASD). However, despite the predicted loss-of-function nature of some of these de novo mutations, the affected individuals are heterozygous carriers, which would suggest that most of these candidate genes are haploinsufficient and/or lead to expression of dominant-negative forms of the protein. Here, we tested this hypothesis with the candidate ASD gene Nuak1 that we previously identified for its role in the development of cortical connectivity. We report that Nuak1 is haploinsufficient in mice with regard to its function in cortical development. Furthermore Nuak1(+/-) mice show a combination of abnormal behavioral traits ranging from defective spatial memory consolidation, defects in social novelty (but not social preference) and abnormal sensorimotor gating. Overall, our results demonstrate that Nuak1 haploinsufficiency leads to defects in the development of cortical connectivity and a complex array of behavorial deficits.
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2. Del Hoyo Soriano L, Thurman AJ, Abbeduto L. {{Specificity: A Phenotypic Comparison of Communication-Relevant Domains Between Youth With Down Syndrome and Fragile X Syndrome}}. {Frontiers in genetics}. 2018; 9: 424.
Despite the shared presence of an intellectual disability (ID), there is a growing literature documenting important phenotypic differences between Down syndrome (DS) and fragile X syndrome (FXS). These conclusions, however, are based on a synthesis across studies, each of which typically includes only measures of a limited number of constructs, and with differing participant characteristics. Firmer conclusions regarding specific phenotypes require a single comprehensive multi-domain assessment of participants with the syndrome groups being well matched on chronological age (CA) and cognitive functioning. The current study was designed to fill this gap by assessing several important cognitive and behavioral domains relevant to communication, such as: structural language skills, false belief understanding, as well as pragmatics and behavioral difficulties, in 30 adolescents of both sexes with DS and 39 males with FXS, matched on CA and nonverbal (NV) cognition. After statistically controlling for NV cognition, we did not find significant syndrome differences in expressive and receptive structural language or false belief understanding. In contrast, participants with DS displayed less stereotyped language and fewer behavioral difficulties compared to males with FXS. Within-syndrome associations among the targeted domains are described. Finally, females with DS were less impaired than males with DS in almost all structural language domains, whereas no significant sex-related differences were observed in NV cognition, false belief understanding, pragmatics, or behavior. Clinical and methodological implications of the findings are discussed.
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3. Fang Q, Aiken CA, Fang C, Pan Z. {{Effects of Exergaming on Physical and Cognitive Functions in Individuals with Autism Spectrum Disorder: A Systematic Review}}. {Games for health journal}. 2018.
The increase in autism spectrum disorder (ASD) population triggers a deep concern within public health. This alarming trend stresses the need for the development of effective strategies that might aid with this growing population. Exergaming has several advantages as an ASD intervention, such as flexible play, a private space for exercise, and diverse types of physical activity. The study aims to analyze the effectiveness of exergaming interventions on individuals with ASD. The systematic review was conducted in accordance with PRISMA guidelines. Studies which employed exergaming interventions on individuals with ASD were considered for inclusion. Exergaming-related changes in participants’ physical and cognitive functions were the main interest of the current review. Ten articles satisfied the predetermined eligibility criteria. Thematic coding categorized the main outcomes into two higher-order themes and five subthemes. The higher-order themes were physical performance and cognitive performance. The emerged subthemes were physical fitness, motor performance, intensity of physical activity, executive function, and self-perception. Following exergame interventions, individuals with ASD indicated significant improvements in physical fitness, executive function, and self-perception. Exergaming also increased participation in moderate-to-vigorous physical activity. In contrast, exergaming indicated small impact on emotional regulation and did not provide adequate opportunities for motor skill development. It is worth noting that only one randomized controlled trial was included in the current review. Future research would require more rigorous study designs to provide reliable evidence on the effectiveness of exergaming interventions for individuals with ASD. Exergaming interventions lead to improved physical and cognitive functions in individuals with ASD. It is suggested that exergaming be used as a feasible supplement to traditional physical activity programs for individuals with ASD.
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4. Lefebvre A, Delorme R, Delanoe C, Amsellem F, Beggiato A, Germanaud D, Bourgeron T, Toro R, Dumas G. {{Alpha Waves as a Neuromarker of Autism Spectrum Disorder: The Challenge of Reproducibility and Heterogeneity}}. {Frontiers in neuroscience}. 2018; 12: 662.
Background: There is no consensus in the literature concerning the presence of abnormal alpha wave profiles in patients with autism spectrum disorder (ASD). This may be due to phenotypic heterogeneity among patients as well as the limited sample sizes utilized. Here we present our results of alpha wave profile analysis based on a sample larger than most of those in the field, performed using a robust processing pipeline. Methods: We compared the alpha waves profiles at rest in children with ASD to those of age-, sex-, and IQ-matched control individuals. We used linear regression and non-parametric normative models using age as covariate forparsing the clinical heterogeneity. We explored the correlation between EEG profiles and the patient’s brain volumes, obtained from structural MRI. We automatized the detection of the alpha peak and visually quality controled our MRI measurements. We assessed the robustness of our results by running the EEG preprocessing with two different versions of Matlab as well as Python. Results: A simple linear regression between peak power or frequency of the alpha waves and the status or age of the participants did not allow to identify any statistically significant relationship. The non-parametric normative model (which took account the non-linear effect of age on the alpha profiles) suggested that participants with ASD displayed more variability than control participants for both frequency and amplitude of the alpha peak (p < 0.05). Independent of the status of the individual, we also observed weak associations (uncorrected p < 0.05) between the alpha frequency, and the volumes of several cortical and subcortical structures (in particular the striatum), but which did not survive correction for multiple testing and changed between analysis pelines. Discussions: Our study did not find evidence for abnormal alpha wave profiles in ASD. We propose, however, an analysis pipeline to perform standardized and automatized EEG analyses on large cohorts. These should help the community to address the challenge of clinical heterogeneity of ASD and to tackle the problems of reproducibility. Lien vers le texte intégral (Open Access ou abonnement)
5. Magan-Maganto M, Canal-Bedia R, Hernandez-Fabian A, Bejarano-Martin A, Fernandez-Alvarez CJ, Martinez-Velarte M, Martin-Cilleros MV, Flores-Robaina N, Roeyers H, Posada de la Paz M. {{Spanish Cultural Validation of the Modified Checklist for Autism in Toddlers, Revised}}. {Journal of autism and developmental disorders}. 2018.
The Modified Checklist for Autism in Toddlers-revised/follow-up (M-CHAT-R/F) was developed to reduce the number of cases requiring telephone verification. The aim of this study was to validate a Spanish version of the M-CHAT-R/F in the Spanish public health system. The M-CHAT-R/F was translated, culturally adapted, and then administered to 6625 children. Of the 39 positive screening cases, 15 children were diagnosed with autism spectrum disorder (ASD) and 24 with non-ASD disorders or delays. The sensitivity was 0.79 and specificity of 0.99. Positive and negative predictive values were 0.39 and 0.99, respectively. These results are similar to the English equivalent, though observed prevalence was lower. This study supports Spanish National Health System policy makers to consider a universal ASD screening program.
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6. Mammarella IC, Cardillo R, Zoccante L. {{Differences in visuospatial processing in individuals with nonverbal learning disability or autism spectrum disorder without intellectual disability}}. {Neuropsychology}. 2018.
OBJECTIVE: Although previous reports produced converging empirical evidence of a core deficit on visuospatial processing in children with a nonverbal learning disability (NLD), few studies compared the visuospatial profile of individuals with an autism spectrum disorder (ASD) or NLD in visuoconstructive and visuospatial working memory tasks. Nor did any of these studies investigate the role of the local bias, typically observed in ASD, when comparing these clinical groups. The present study aimed to analyze whether NLD and ASD share any characteristics. METHOD: A group of participants with NLD (n = 17) was compared with another group who had ASD (n = 17) without intellectual disability (ID), and without a peak in visuospatial intelligence, and with a control group (n = 17). Participants aged from 8 to 18 years performed a visuoconstructive and a visuospatial working memory task in which global-local processing styles were manipulated. RESULTS: The analysis of their visuospatial processing clearly distinguished between the neuropsychological profiles of the group with ASD without ID and the group with NLD: the latter performed less well than the former in all domains. The participants with ASD without ID had a more heterogeneous visuospatial profile, showing a diminished sensitivity to perceptual cohesiveness only in the visuoconstructive task. CONCLUSIONS: Examining different visuospatial domains and manipulating the cohesiveness of the stimuli might be useful for better discriminating between NLD and ASD without ID. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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7. Rydzewska E, Hughes-McCormack LA, Gillberg C, Henderson A, MacIntyre C, Rintoul J, Cooper SA. {{Prevalence of sensory impairments, physical and intellectual disabilities, and mental health in children and young people with self/proxy-reported autism: Observational study of a whole country population}}. {Autism : the international journal of research and practice}. 2018: 1362361318791279.
This study investigated the comorbid conditions in a whole country population of children/young people aged 0-24 years with and without autism. Data were drawn from Scotland’s Census 2011. We calculated the percentage with autism, their extent of comorbid conditions, odds ratio (with 95% confidence intervals) of autism predicting comorbidities, adjusted for age and gender, and odds ratio for age and gender predicting comorbidities within the cohort with autism. A total of 25,063/1,548,819 (1.6%) had autism: 19,880 (79.3%) males and 5183 (20.7%) females. Autism had an odds ratio of 5.4 (5.1-5.6) for predicting deafness/partial hearing loss, odds ratio of 8.9 (8.1-9.7) for blindness/partial sight loss, odds ratio of 49.7 (38.1-64.9) for intellectual disabilities, odds ratio of 15.7 (13.4-18.5) for mental health conditions, odds ratio of 15.8 (14.1-17.8) for physical disability and odds ratio of 3.9 (3.8-4.0) for other conditions. Females with autism were more likely to have each additional condition than males, including intellectual disabilities, suggesting they may have more severe autism than males and adding evidence that autism may be currently underdiagnosed in more intellectually able females. These conditions are disabling and have a significant impact on long-term quality of life; their coexistence with autism adds extra complexity. It is important to raise clinicians’ awareness of this extent of comorbidity, and to have accurate prevalence data to plan prevention and intervention measures, and to follow health inequality trends.
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8. Tu Z, Zhao H, Li B, Yan S, Wang L, Tang Y, Li Z, Bai D, Li C, Lin Y, Li Y, Liu J, Xu H, Guo X, Jiang YH, Zhang YQ, Li XJ. {{CRISPR/Cas9-mediated disruption of SHANK3 in monkey leads to drug-treatable autism-like symptoms}}. {Human molecular genetics}. 2018.
Monogenic mutations in the SHANK3 gene, which encodes a postsynaptic scaffold protein, play a causative role in autism spectrum disorder (ASD). Although a number of mouse models with Shank3 mutations have been valuable for investigating the pathogenesis of ASD, species-dependent differences in behaviors and brain structures post considerable challenges to use small animals to model ASD and to translate experimental therapeutics to the clinic. We have used CRISPR/Cas9 to generate a cynomolgus monkey model by disrupting SHANK3 at exon 6 and 12. Analysis of the live mutant monkey revealed the core behavioral abnormalities of ASD, including impaired social interaction and repetitive behaviors, and reduced brain network activities detected by positron-emission tomography (PET). Importantly, these abnormal behaviors and brain activities were alleviated by the antidepressant fluoxetine treatment. Our findings provide the first demonstration that the genetically modified non-human primate can be used for translational research of therapeutics for ASD.
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9. Vivanti G, Hamner T, Lee NR. {{Neurodevelopmental Disorders Affecting Sociability: Recent Research Advances and Future Directions in Autism Spectrum Disorder and Williams Syndrome}}. {Current neurology and neuroscience reports}. 2018; 18(12): 94.
PURPOSE OF REVIEW: In this review, we summarize current knowledge and hypotheses on the nature of social abnormalities in autism spectrum disorder (ASD) and Williams syndrome (WS). RECENT FINDINGS: Social phenotypes in ASD and WS appear to reflect analogous disruptions in social cognition, and distinct patterns of social motivation, which appears to be reduced in ASD and enhanced in WS. These abnormalities likely originate from heterogeneous vulnerabilities that disrupt the interplay between domain-general and social domain-specific cognitive and motivational processes during early development. Causal pathways remain unclear. Advances and research gaps in our understanding of the social phenotypes in ASD and WS highlight the importance of (1) parsing the construct of sociability, (2) adopting a developmental perspective, (3) including samples that are representative of the spectrum of severity within ASD and WS in neuroscientific research, and (4) adopting transdiagnostic treatment approaches to target shared areas of impairment across diagnostic boundaries.
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10. Vllasaliu L, Jensen K, Dose M, Hagenah U, Hollmann H, Kamp-Becker I, Lechmann C, Poustka L, Sinzig J, Spitzcok von Brisinski I, Tebartz van Elst L, Will D, Vogeley K, Freitag CM. {{[The diagnostics of autism spectrum disorder in children, adolescents and adults: Overview of the key questions and main results of the first part of the German AWMF-S3-clinical guideline]}}. {Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie}. 2018: 1-12.
The diagnostics of autism spectrum disorder in children, adolescents and adults: Overview of the key questions and main results of the first part of the German AWMF-S3-clinical guideline Abstract. BACKGROUND: Autism spectrum disorders (ASD) include ICD-10 diagnoses of childhood autism, Asperger syndrome, and atypical autism; there is a lifetime prevalence of ~1 %. The aim of the evidence-based clinical guideline (AWMF-S3-Guideline) is to summarize the current evidence concerning diagnostic and therapeutic processes for professionals working in healthcare and social welfare and to provide consensus on clinical recommendations. The present study summarizes the most important results of the diagnostic part of this guideline. METHOD: The guideline group comprised 14 clinical and scientific expert associations from the German healthcare system, in addition to representatives of relatives and patients. Recommendations were based on results of a systematic literature search, data extraction, the evaluation of study quality, and, if possible, meta-analytic aggregation of included data in combination with the clinical expertise of the respective representatives. Consensus-based recommendations were determined via nominal group technique. RESULTS: The AWMF-S3-Clinical Guideline, Diagnostic Part, summarizes current research on this topic. The main focus is put on the question of obligatory versus redundant diagnostic procedures. After a general introduction to the clinical picture of ASD, essential aspects like obtaining the medical history, the effective use of screening and diagnostic instruments, medical examination, the full diagnostic work-up as well as communicating the diagnostic results to relatives and patients are described in detail. We also conducted a meta-analysis on the stability of early diagnosis. CONCLUSION: This first part of the ASD guideline offers users the opportunity to inform themselves about the background of ASD as well as evidence-based and broadly consented information on the correct diagnostic process of ASD from infancy to adulthood.
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11. Wang H, Yin YX, Gong DM, Hong LJ, Wu G, Jiang Q, Wang CK, Blinder P, Long S, Han F, Lu YM. {{Cathepsin B inhibition ameliorates leukocyte-endothelial adhesion in the BTBR mouse model of autism}}. {CNS neuroscience & therapeutics}. 2018.
AIMS: Autism spectrum disorder (ASD) is a wide range of neurodevelopmental disorders involving deficits in social interaction and communication. Unfortunately, autism remains a scientific and clinical challenge owing to the lack of understanding the cellular and molecular mechanisms underlying it. This study aimed to investigate the pathophysiological mechanism underlying leukocyte-endothelial adhesion in autism-related neurovascular inflammation. METHODS: Male BTBR T+tf/J mice were used as an autism model. The dynamic pattern of leukocyte-endothelial adhesion in mouse cerebral vessels was detected by two-photon laser scanning microscopy (TPLSM). Using FACS, RT-PCR, and Western blotting, we explored the expression of cell adhesion molecules, the mRNA expression of endothelial chemokine, the protein levels of cathepsin B, and inflammatory mediators. RESULTS: We found a significant increase in leukocyte-endothelial adhesion in BTBR mice, accompanied by elevated expression of the adhesion molecule neutrophils CD11b and endothelial ICAM-1. Our data further indicate that elevated neutrophil cathepsin B levels contribute to elevated endothelial chemokine CXCL7 levels in BTBR mice. The pharmacological inhibition of cathepsin B reverses the enhanced leukocyte-endothelial adhesion in the cerebral vessels of autistic mice. CONCLUSION: Our results revealed the prominent role of cathepsin B in modulating leukocyte-endothelial adhesion during autism-related neurovascular inflammation and identified a promising novel approach for autism treatment.
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12. Won DC, Feldman HM, Huffman LC. {{Sleep Problem Detection and Documentation in Children With ASD and ADHD by Developmental-Behavioral Pediatricians: A DBPNet Study}}. {Journal of developmental and behavioral pediatrics : JDBP}. 2018.
OBJECTIVE: To determine the percentage of children with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and combined ASD + ADHD who had sleep problems documented by developmental-behavioral pediatricians at diagnostic and follow-up visits at 12 US academic medical centers comprising the Developmental-Behavioral Pediatrics Research Network (DBPNet) and to identify the predictors of sleep problem documentation. METHODS: Developmental-behavioral pediatricians completed encounter forms that covered sociodemographic, medical, clinician, and visit factors. There was 1 dependent variable, sleep problem documentation, for which 4 definitions were developed (Model 1 = Sleep Disorder coded; Model 2 = Sleep Disorder or polysomnogram coded; Model 3 = Sleep Disorder, polysomnogram, or sleep medication coded; and Model 4 = Sleep Disorder, polysomnogram, sleep medication, or clonidine coded). RESULTS: Sleep problem documentation was 14.1% for Model 1, 15.2% for Model 2, 17.3% for Model 3, and 19.7% for Model 4. All values were lower (p < 0.001) than the reported prevalence of sleep problems in these conditions. For Model 4, predictors of sleep problem documentation were age group, ethnicity, medical insurance type, and DBPNet site. CONCLUSION: Developmental-behavioral pediatricians in DBPNet under-reported sleep problems in children with ASD and ADHD. Variation among sites was substantial. Care plans for children with ASD and ADHD should specify which treating clinician(s) monitors sleep issues. Lien vers le texte intégral (Open Access ou abonnement)
