1. Carrette LLG, Blum R, Ma W, Kelleher RJ, 3rd, Lee JT. {{Tsix-Mecp2 female mouse model for Rett syndrome reveals that low-level MECP2 expression extends life and improves neuromotor function}}. {Proceedings of the National Academy of Sciences of the United States of America}. 2018; 115(32): 8185-90.
Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by a mutation in the X-linked methyl-CpG-binding protein 2 (MECP2). There is currently no disease-specific treatment, but MECP2 restoration through reactivation of the inactive X (Xi) has been of considerable interest. Progress toward an Xi-reactivation therapy has been hampered by a lack of suitable female mouse models. Because of cellular mosaicism due to random X-chromosome inactivation (XCI), Mecp2(+/-) heterozygous females develop only mild RTT. Here, we create an improved female mouse model by introducing a mutation in Tsix, the antisense regulator of XCI allelic choice. Tsix-Mecp2 mice show reduced MECP2 mosaicism and closely phenocopy the severely affected Mecp2-null males. Tsix-Mecp2 females demonstrate shortened lifespan, motor weakness, tremors, and gait disturbance. Intriguingly, they also exhibit repetitive behaviors, as is often seen in human RTT, including excessive grooming and biting that result in self-injury. With a Tsix allelic series, we vary MECP2 levels in brain and demonstrate a direct, but nonlinear correlation between MECP2 levels and phenotypic improvement. As little as 5-10% MECP2 restoration improves neuromotor function and extends lifespan five- to eightfold. Our study thus guides future pharmacological strategies and suggests that partial MECP2 restoration could have disproportionate therapeutic benefit.
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2. Eslami N, Movahed T, Asadi M. {{Parents’ Perceptions of the Oral Health-related Quality of Life of their Autistic Children in Iran}}. {The Journal of clinical pediatric dentistry}. 2018.
OBJECTIVES: The aim of this study was to evaluate parents’ perception of the oral health-related quality of life (OHRQoL) of autistic children in Iran, and to determine the quality of life of their families in relation to child’ oral health status. STUDY DESIGN: 70 families with at least one child with autism, and 70 families with normal children were enrolled. Parents’ perceptions of the OHRQoL of children were assessed using pre-validated PedsQL oral health scale questionnaire. PedsQL Family Impact Module questionnaire was also used to evaluate the impact of having an autistic child on the quality of life of their families. Both of the questionnaires were filled by parents. Parents of children with autism spectrum filled a separate questionnaire for the sibling of the autistic child. In the control families, child-reported PedsQL oral health scale questionnaire was also filled by the child himself/herself. Mann-Whitney U-test, and chi-square were used for statistical analysis. RESULTS: There was a significant difference in the mean total score of PedsQL oral health scale questionnaire between autistics and controls. Parents of normal children reported more oral problems (p<0.001). There was not a significant difference in the mean total score of PedsQL Family Impact Module questionnaire between the families of autistics and controls in the last 7 and 30 days. CONCLUSION: According to parents' point of view, oral health-related quality of life of autistic children was better than normal children. However, parents of autistic children had more problems in the social and communication issues. Lien vers le texte intégral (Open Access ou abonnement)
3. Gotham KO, Siegle GJ, Han GT, Tomarken AJ, Crist RN, Simon DM, Bodfish JW. {{Pupil response to social-emotional material is associated with rumination and depressive symptoms in adults with autism spectrum disorder}}. {PLoS One}. 2018; 13(8): e0200340.
BACKGROUND: Autism spectrum disorder (ASD) is marked by repetitive thinking and high rates of depression. Understanding the extent to which repetitive negative thinking in ASD reflects autistic stereotypy versus general depressive thinking patterns (e.g., rumination) could help guide treatment research to improve emotional health in ASD. We compared associations between rumination, depressive symptoms, and pupil response to social-emotional material in adults with ASD and typically developing (TD) adults with and without depression. METHODS: N = 53 verbally fluent young adults were recruited to three cohorts: ASD, n = 21; TD-depressed, n = 13; never-depressed TD-controls, n = 19. Participants completed Ruminative Response Scale and Beck Depression Inventory self-reports and a passive-viewing task employing emotionally-expressive faces, during which pupillary motility was assessed to quantify cognitive-affective load. Main and interactive effects of cohort, emotion condition, and time on pupil amplitude were tested via a linear mixed effects analysis of variance using restricted maximum likelihood estimation. Similar procedures were used to test for effects of rumination and depressive symptoms on pupil amplitude over time within ASD. RESULTS: Responsive pupil dilation in the ASD cohort tended to be significantly lower than TD-depressed initially but increased to comparable levels by trial end. When viewing sad faces, individuals with ASD who had higher depression scores resembled TD-depressed participants’ faster, larger, and sustained pupil response. Within ASD, depressive symptoms uniquely predicted early pupil response to sad faces, while rumination and depression scores each independently predicted sustained pupil response. CONCLUSIONS: People with elevated depressive symptoms appear to have faster and greater increases in pupil-indexed neural activation following sad stimuli, regardless of ASD status, suggesting the utility of conceptualizing rumination as depression-like in treatment. Ruminative processes may increase more slowly in ASD, suggesting the potential utility of interventions that decrease reactions before they are uncontrollable. Findings also reinforce the importance of testing for effects of internalizing variables in broader ASD research.
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4. Hamad AF, Alessi-Severini S, Mahmud SM, Brownell M, Kuo IF. {{Early childhood antibiotics use and autism spectrum disorders: a population-based cohort study}}. {International journal of epidemiology}. 2018.
Background: Changes in microbiota composition as a result of antibiotics use in early life has been proposed as a possible contributor in the aetiology of autism spectrum disorders (ASD). We aimed to examine the association between early life antibiotic exposure and risk of ASD. Methods: This was a population-based cohort study which included all live births in Manitoba, Canada, between 1 April 1998 and 31 March 2016. We used administrative health data from the Manitoba Population Research Data Repository. Exposure was defined as having filled one or more antibiotic prescription during the first year of life. The main outcome was ASD diagnosis. Cox proportional hazards regression models were used to estimate the risk of developing ASD in the overall population and in a sibling cohort. Results: Of all subjects in the cohort (n = 214 834), 94 024 (43.8%) filled an antibiotic prescription during the first year of life. During follow-up, 2965 children received an ASD diagnosis. Compared with children who did not use antibiotics during the first year of life, those who received antibiotics had a reduced risk of ASD [adjusted hazardz ratio (HR) 0.91, 95% confidence interval (CI) 0.84-0.99). Number of treatment courses and cumulative duration of antibiotic exposure were not associated with ASD. In the sibling-controlled analysis, early life antibiotic exposure was not associated with ASD (adjusted HR 1.03, 95% CI 0.86-1.23). Conclusions: Our findings suggested no clinically significant association between early life antibiotics exposure and risk of autism spectrum disorders, and should provide reassurance to concerned prescribers and parents.
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5. Heymann P, Northrup JB, West KL, Parlade MV, Leezenbaum NB, Iverson JM. {{Coordination is key: Joint attention and vocalisation in infant siblings of children with Autism Spectrum Disorder}}. {Int J Lang Commun Disord}. 2018.
BACKGROUND: Research indicates that social communicative behaviours develop atypically during the second year in Autism Spectrum Disorder (ASD). This study evaluated whether these behaviours also differed in the extent to which they were coordinated across modalities. AIMS: To measure joint attention behaviours (e.g., gaze shifts, gestures), vocalisations and their coordination among a cohort of infants with an older sibling with ASD (heightened risk-HR). METHODS & PROCEDURES: This prospective longitudinal study examined 50 HR infants at 14, 18 and 24 months. The Early Social Communication Scales (ESCS)-a structured toy-play task that assesses infant joint attention behaviour-was administered to infants at each age point in the home. Infants’ joint attention behaviours, vocalisations and instances where they overlapped were coded from videos. At 36 months, nine infants received an ASD diagnosis (HR-ASD), 15 had a significant language delay (HR-LD) and 26 were classified no diagnosis (HR-ND). OUTCOMES & RESULTS: Findings revealed that HR-ASD infants produced fewer advanced joint attention behaviours, and their vocalisations were less frequent and less advanced than HR-LD and HR-ND infants. Notably, HR-ASD infants also coordinated these behaviours together less frequently than their HR peers. CONCLUSIONS & IMPLICATIONS: Differences in the coordination of early communicative behaviours may have negative cascading effects on social and language development for infants who develop ASD. Current intervention practices may be complemented by efforts to increase the coordinated quality of communicative behaviours.
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6. Johnson CR, Brown K, Hyman SL, Brooks MM, Aponte C, Levato L, Schmidt B, Evans V, Huo Z, Bendixen R, Eng H, Sax T, Smith T. {{Parent Training for Feeding Problems in Children With Autism Spectrum Disorder: Initial Randomized Trial}}. {Journal of pediatric psychology}. 2018.
Objective: Many children with autism spectrum disorder (ASD) have feeding and mealtime problems. To address these, we conducted a pilot randomized trial of a new 11-session, individually delivered parent training program that integrated behavioral strategies and nutritional guidance (PT-F). Methods: Forty-two young children (age: 2 to 7-11 years) with ASD and feeding problems were assigned to 11 sessions of PT-F intervention over 20 weeks or a waitlist control. Outcomes included attendance, parent satisfaction, therapist fidelity, and preliminary assessments of child and parent outcomes. Results: Of the 21 PT-F families, attendance was high (85%) as was parent satisfaction (94% would recommend to others). Treatment fidelity was also high (97%-therapist integrity; 94%-parent adherence). Compared with waitlist, children whose parents participated in PT-F showed significantly greater reductions on the two parent-completed primary outcomes (Brief Autism Mealtime Behavior Inventory-Revised; Twald = -2.79; p = .003; About Your Child’s Eating; Twald = -3.58; p = .001). On the independent evaluator-completed secondary eating outcome, the Clinical Global Impression-Improvement, 48.8% of the participants in PT-F were rated as « responders » compared with 0% in waitlist (p = .006). General child disruptive behavior outcomes decreased more in PT-F but not significantly. Parent outcomes of caregiver stress showed nonsignificant trends favoring PT-F with moderate to small effect sizes. Conclusions: This trial provides evidence for feasibility, satisfaction, and fidelity of implementation of PT-F for feeding problems in young children with ASD. Feeding outcomes also appeared favorable and lends support for conducting a larger efficacy trial.
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7. Kraan CM, Godler DE, Amor DJ. {{Epigenetics of fragile X syndrome and fragile X-related disorders}}. {Dev Med Child Neurol}. 2018.
The fragile X mental retardation 1 gene (FMR1)-related disorder fragile X syndrome (FXS) is the most common heritable form of cognitive impairment and the second most common cause of comorbid autism. FXS usually results when a premutation trinucleotide CGG repeat in the 5′ untranslated region of the FMR1 gene (CGG 55-200) expands over generations to a full mutation allele (CGG >200). This expansion is associated with silencing of the FMR1 promoter via an epigenetic mechanism that involves DNA methylation of the CGG repeat and the surrounding regulatory regions. Decrease in FMR1 transcription is associated with loss of the FMR1 protein that is needed for typical brain development. The past decade has seen major advances in our understanding of the genetic and epigenetic processes that underlie FXS. Here we review these advances and their implications for diagnosis and treatment for individuals who have FMR1-related disorders.
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8. Lord C, Elsabbagh M, Baird G, Veenstra-Vanderweele J. {{Autism spectrum disorder}}. {Lancet (London, England)}. 2018; 392(10146): 508-20.
Autism spectrum disorder is a term used to describe a constellation of early-appearing social communication deficits and repetitive sensory-motor behaviours associated with a strong genetic component as well as other causes. The outlook for many individuals with autism spectrum disorder today is brighter than it was 50 years ago; more people with the condition are able to speak, read, and live in the community rather than in institutions, and some will be largely free from symptoms of the disorder by adulthood. Nevertheless, most individuals will not work full-time or live independently. Genetics and neuroscience have identified intriguing patterns of risk, but without much practical benefit yet. Considerable work is still needed to understand how and when behavioural and medical treatments can be effective, and for which children, including those with substantial comorbidities. It is also important to implement what we already know and develop services for adults with autism spectrum disorder. Clinicians can make a difference by providing timely and individualised help to families navigating referrals and access to community support systems, by providing accurate information despite often unfiltered media input, and by anticipating transitions such as family changes and school entry and leaving.
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9. Lowe MX, Stevenson RA, Barense MD, Cant JS, Ferber S. {{Relating the perception of visual ensemble statistics to individual levels of autistic traits}}. {Attention, perception & psychophysics}. 2018.
Integrating information across the visual field into an ensemble (e.g., seeing the forest from the trees) is an effective strategy to efficiently process the visual world, and one that is often impaired in autism spectrum disorder. Individual differences in sensory processing predict ensemble encoding, providing a potential mechanism for differing perceptual strategies across individuals, and possibly across diagnostic groups exhibiting atypical sensory processing. Here, we explore whether ensemble encoding is associated with traits associated with autism spectrum disorder (ASD). Participants (N=68) were presented with an ensemble display consisting of circles of varying sizes and colors, and were asked to remember the size of the red and blue circles, while ignoring the green circles. Participants were then cued to a target location after a brief delay, and instructed to report the remembered size of the circle they had previously viewed in that location, as ensemble information commonly biases memory for individual objects toward the probed mean of a set of similar objects. The Autism-spectrum Quotient (AQ) was completed to measure each individual’s level of autistic traits. We found that an individual’s level of ensemble perception, measured as their bias toward the probed mean, was negatively associated with a higher level of ASD traits. These results suggest that individuals with higher levels of ASD traits are less likely to integrate perceptual information. These findings may shed light on different perceptual processing within the autism spectrum, and provide insight into the relationship between individual differences and ensemble encoding.
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10. Pascual-Belda A, Diaz-Parra A, Moratal D. {{Evaluating Functional Connectivity Alterations in Autism Spectrum Disorder Using Network-Based Statistics}}. {Diagnostics (Basel, Switzerland)}. 2018; 8(3).
The study of resting-state functional brain networks is a powerful tool to understand the neurological bases of a variety of disorders such as Autism Spectrum Disorder (ASD). In this work, we have studied the differences in functional brain connectivity between a group of 74 ASD subjects and a group of 82 typical-development (TD) subjects using functional magnetic resonance imaging (fMRI). We have used a network approach whereby the brain is divided into discrete regions or nodes that interact with each other through connections or edges. Functional brain networks were estimated using the Pearson’s correlation coefficient and compared by means of the Network-Based Statistic (NBS) method. The obtained results reveal a combination of both overconnectivity and underconnectivity, with the presence of networks in which the connectivity levels differ significantly between ASD and TD groups. The alterations mainly affect the temporal and frontal lobe, as well as the limbic system, especially those regions related with social interaction and emotion management functions. These results are concordant with the clinical profile of the disorder and can contribute to the elucidation of its neurological basis, encouraging the development of new clinical approaches.
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11. Rafee Y, Burrell K, Cederna-Meko C. {{Lessons in early identification and treatment from a case of disabling vitamin C deficiency in a child with autism spectrum disorder}}. {International journal of psychiatry in medicine}. 2018: 91217418791443.
Background Autism spectrum disorder is a heterogenous neurodevelopmental condition accompanied by a variety of associated features. Case reports suggest one such associated feature, food selectivity, increases risk for nutritional deficiencies; however, little attention has been given to prevent and treat nutritional deficiencies in youth with autism spectrum disorder. Method Single case report. Results This single case report presents a child with autism spectrum disorder and food selectivity difficulties that resulted in severe vitamin C deficiency. Although eventually corrected, the nutritional deficiency was debilitating, required invasive interventions, and resulted in significant social/emotional and economic costs. Conclusions We review the course of treatment and highlight strategies to prevent and more effectively treat nutritional deficiencies in youth with autism spectrum disorder.
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12. Raz R, Kioumourtzoglou MA, Weisskopf MG. {{Live Birth Bias and Observed Associations between Air Pollution and Autism}}. {American journal of epidemiology}. 2018.
A recent analysis found that exposure to air pollution in specific pregnancy weeks is negatively associated with risk of autism spectrum disorder (ASD) when mutually adjusted for postnatal air pollution exposure. In this commentary, we describe two possible selection bias processes that may lead to such results, both related to live birth bias, i.e. the inevitable restriction of the analyzed sample to live births. The first mechanism is described using a directed acyclic graph and relates to the chance of live birth being a common consequence of both exposure to air pollution and another risk factor of ASD. The second mechanism involves preferential depletion of fetuses susceptible to ASD in the higher air pollution exposure group. We further discuss the assumptions underlying these processes and their causal structures, their plausibility, and other studies where similar phenomenon may have occurred.
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13. Wang Y, Zhao S, Liu X, Zheng Y, Li L, Meng S. {{Oxytocin improves animal behaviors and ameliorates oxidative stress and inflammation in autistic mice}}. {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}. 2018; 107: 262-9.
OBJECTIVE: Autism is a neurodevelopmental disorder which significantly impacts the quality of people’s life. Oxytocin is a hormone impacting the social cognition and interpersonal trust. In this study, we aimed to explore the role of oxytocin in autism. METHODS: Autistic mice models were established by valproate. Animal behaviors were assessed by open field test, tail suspension test, marble burying test and three-chamber social interaction test. Oxidative stress was evaluated by the levels or activities of malondialdehyde, superoxide dismutase, glutathion peroxidase, reduced glutathione and reactive oxygen species. Inflammation was assessed by the levels of tumor necrosis factor-alpha, interleukin-1beta and interleukin-6. The number of activated microglia was detected by immunofluorescence with an Iba-1 antibody. RESULTS: Our results showed that oxytocin improved the behaviors of autistic mice, with less anxiety, depression and repetitive behavior, and ameliorated social interaction. Further study showed that the elevated oxidative stress and inflammation in autistic mice were alleviated after treatment of oxytocin. CONCLUSION: Our study demonstrates that oxytocin treatment ameliorates autism in a mouse model, maybe through its modulation on oxidative stress and inflammation. It is indicated that oxytocin may beneficial to autism.
