1. Cannell JJ. {{Vitamin D and autism, what’s new?}}. {Rev Endocr Metab Disord}. 2017.
An increasing amount of evidence points to the possibility that gestational and early childhood vitamin D deficiency [25(OH)D < 40 ng/ml] cause some cases of autism. Vitamin D is metabolized into a seco-steroid hormone that regulates about 3% of the 26,000 genes in the coding human genome. It is also a neurosteroid that is active in brain development, having effects on cellular proliferation, differentiation, calcium signaling, neurotrophic and neuroprotective actions; it also appears to have an effect on neurotransmission and synaptic plasticity. Children who are, or who are destined to become, autistic have lower 25(OH)D levels at 3 months of gestation, at birth and at age 8 compared to their unaffected siblings. Two open label trials found high dose vitamin D improves the core symptoms of autism in about 75% of autistic children. A few of the improvements were remarkable. The vitamin D doses used in these children were 300 IU/KG/day up to a maximum of 5000 IU/day (highest final 25(OH)D level reached was 45 ng/ml). The other study used 150,000 IU/month IM as well as 400 IU/day [highest final 25(OH)D level was 52 ng/ml]. These two open label trials were recently confirmed with a randomized controlled trial (RCT) using 300 IU/kg/day with a maximum of 5000 IU/day and resulted in effects similar to the two open label studies. In terms of prevention, a recent small study showed vitamin D supplementation during pregnancy (5000 IU/day) and during infancy and early childhood (1000 IU/day) significantly reduced the expected incidence of autism in mothers who already had one autistic child from 20% to 5%. Vitamin D is safe; for example, over the last 15 years, Poison Control reports there have been approximately 15,000 cases of vitamin D overdose. However only three of these 15,000 people developed clinical toxicity and no one died. Given those facts, practitioners might consider treating autism with 300 IU/kg/day, and seek to prevent autism by supplementing pregnant and lactating women (5000 IU/day) and infants and young children (150 IU/kg/day) checking 25(OH)D levels every 3 months. These doses will increase 25(OH)D blood levels to those recommended by the Endocrine Society. As the American Academy of Pediatrics recommends vitamin D supplementation during infancy and childhood, pediatricians and family practitioners should evaluate the current evidence on autism and vitamin D and act accordingly. Lien vers le texte intégral (Open Access ou abonnement)
2. Cohrs AC, Leslie DL. {{Depression in Parents of Children Diagnosed with Autism Spectrum Disorder: A Claims-Based Analysis}}. {J Autism Dev Disord}. 2017.
Previous studies showing that Autism Spectrum Disorder (ASD) in children can have secondary effects on the child’s parents are limited by small sample sizes and parent self-report. We examined the odds of depression in parents of children with ASD compared to parents of children without ASD using a large national claims database. Mothers (OR 2.95, 95% CI 2.81-3.09) and fathers (OR 2.41, 95% CI 2.25-2.58) of children with ASD were more likely to have a diagnosis of depression than parents of children without ASD. Odds of depression also increased when there was more than one child with ASD in the family and with child age. Study results reinforce the benefits of support and education for parents of children with ASD.
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3. Dimian AF, Botteron KN, Dager SR, Elison JT, Estes AM, Pruett JR, Jr., Schultz RT, Zwaigenbaum L, Piven J, Wolff JJ. {{Potential Risk Factors for the Development of Self-Injurious Behavior among Infants at Risk for Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2017.
Prevalence of self-injurious behavior (SIB) is as high as 50% among children with autism spectrum disorder (ASD). Identification of risk factors for the development of SIB is critical to early intervention and prevention. However, there is little empirical research utilizing a prospective design to identify early risk factors for SIB. The purpose of this study was to evaluate behavioral characteristics predicting SIB at age 2 years among 235 infants at high familial risk for ASD. Logistic regression results indicated that presence of SIB or proto-SIB and lower developmental functioning at age 12 months significantly predicted SIB at 24 months. A pattern of persistent SIB over this period was associated with a diagnosis of autism and poorer cognitive and adaptive outcomes.
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4. Hutchins TL, Deraway C, Prelock P, O’Neill A. {{Mothers’ and Children’s Story-Telling: A Study of Dyads with Typically Developing Children and Children with ASD}}. {J Autism Dev Disord}. 2017.
The production of specific mental state terms types and functions by caregivers and their TD children and caregivers and their children with ASD were assessed in two contexts: a parent’s story-telling task and a child’s story-telling task. Caregivers of children with ASD produced less causal talk and proportionally less desire and cognitive talk than did caregivers of TD children. When focusing only on variation in our ASD sample, caregivers’ and children’s production of different mental state references varied with context and were predicted by different child characteristics (i.e., theory of mind, autism severity, language level). We conclude that caregivers are likely adjusting different aspects of mental state input depending on different aspects of child development although these adjustments may not always be optimal.
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5. Ioannou C, Zein ME, Wyart V, Scheid I, Amsellem F, Delorme R, Chevallier C, Grezes J. {{Shared mechanism for emotion processing in adolescents with and without autism}}. {Sci Rep}. 2017; 7: 42696.
Although, the quest to understand emotional processing in individuals with Autism Spectrum Disorders (ASD) has led to an impressive number of studies, the picture that emerges from this research remains inconsistent. Some studies find that Typically Developing (TD) individuals outperform those with ASD in emotion recognition tasks, others find no such difference. In this paper, we move beyond focusing on potential group differences in behaviour to answer what we believe is a more pressing question: do individuals with ASD use the same mechanisms to process emotional cues? To this end, we rely on model-based analyses of participants’ accuracy during an emotion categorisation task in which displays of anger and fear are paired with direct vs. averted gaze. Behavioural data of 20 ASD and 20 TD adolescents revealed that the ASD group displayed lower overall performance. Yet, gaze direction had a similar impact on emotion categorisation in both groups, i.e. improved accuracy for salient combinations (anger-direct, fear-averted). Critically, computational modelling of participants’ behaviour reveals that the same mechanism, i.e. increased perceptual sensitivity, underlies the contextual impact of gaze in both groups. We discuss the specific experimental conditions that may favour emotion processing and the automatic integration of contextual information in ASD.
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6. Johnston KH, Iarocci G. {{Are Generalized Anxiety and Depression Symptoms Associated with Social Competence in Children with and without Autism Spectrum Disorder?}}. {J Autism Dev Disord}. 2017.
Generalized anxiety and depression symptoms may be associated with poorer social outcomes among children with Autism Spectrum Disorder (ASD) without intellectual disability. The goal of this study was to examine whether generalized anxiety and depression symptoms were associated with social competence after accounting for IQ, age, and gender in typically developing children and in children with ASD. Results indicated that for the TD group, generalized anxiety and depression accounted for 38% of the variance in social competence and for children with ASD, they accounted for 29% of the variance in social competence. However, only depression accounted for a significant amount of the variance. The findings underscore the importance of assessing the social impact of internalizing symptoms in children with ASD.
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7. Long JJ, Butchart M, Brown M, Bain J, McMillan A, Karatzias T. {{Improving vision awareness in autism services: Evaluation of a dedicated education programme for support practitioners}}. {J Appl Res Intellect Disabil}. 2017.
BACKGROUND: The research reported here sought to evaluate whether a dedicated education programme in vision awareness improved the knowledge and skills of autism support practitioners in identifying visual impairment in autistic people with intellectual disabilities and providing better support to those individuals identified as visually impaired. METHODS: Researchers undertook a mixed methods evaluation. A survey questionnaire was devised and administered before and after training and focus groups were undertaken in order to gain qualitative data relating how practitioners implemented their learning in practice. RESULTS: Knowledge confidence and practice confidence scores of participants were significantly improved by the programme, which maintained its impact one year on. Practitioners reported increased access to optometry, changes to support practice and improvements to service environments as a result of the training. CONCLUSION: Autism support practitioners’ skills in identifying and supporting people with visual impairments were demonstrably enhanced through dedicated vision training.
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8. Ogawa S, Lee YA, Yamaguchi Y, Shibata Y, Goto Y. {{Associations of acute and chronic stress hormones with cognitive functions in autism spectrum disorder}}. {Neuroscience}. 2017; 343: 229-39.
Extensive studies have reported cognitive abnormalities in neurodevelopmental disorders, such as autism spectrum disorder (ASD). Another line of evidence suggests that stress also affects cognitive functions. In this study, we investigated whether there were associations between stress hormones and cognitive functions in ASD and typically developing (TD) children. Cognitive functions in ASD and TD children were evaluated with a battery of psychological tests for working memory, behavioral flexibility, and social cognition for emotional assessments of others. ASD children exhibited higher hair and salivary cortisol, which reflects chronic and acute stress hormone levels of subjects, respectively, than TD children. Autism-spectrum quotient (AQ) was positively correlated with hair cortisol and the scores of Spence Children’s Anxiety Scale in ASD children. In addition, a negative correlation was present between spatial working memory performance and hair cortisol in ASD, but not in TD, children. These results suggest that chronic stress hormone elevation may have relationships with some aspects of cognitive dysfunction in ASD subjects.
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9. Sethna F, Feng W, Ding Q, Robison AJ, Feng Y, Wang H. {{Enhanced expression of ADCY1 underlies aberrant neuronal signalling and behaviour in a syndromic autism model}}. {Nat Commun}. 2017; 8: 14359.
Fragile X syndrome (FXS), caused by the loss of functional FMRP, is a leading cause of autism. Neurons lacking FMRP show aberrant mRNA translation and intracellular signalling. Here, we identify that, in Fmr1 knockout neurons, type 1 adenylyl cyclase (Adcy1) mRNA translation is enhanced, leading to excessive production of ADCY1 protein and insensitivity to neuronal stimulation. Genetic reduction of Adcy1 normalizes the aberrant ERK1/2- and PI3K-mediated signalling, attenuates excessive protein synthesis and corrects dendritic spine abnormality in Fmr1 knockout mice. Genetic reduction of Adcy1 also ameliorates autism-related symptoms including repetitive behaviour, defective social interaction and audiogenic seizures. Moreover, peripheral administration of NB001, an experimental compound that preferentially suppresses ADCY1 activity over other ADCY subtypes, attenuates the behavioural abnormalities in Fmr1 knockout mice. These results demonstrate a connection between the elevated Adcy1 translation and abnormal ERK1/2 signalling and behavioural symptoms in FXS.
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10. Shpyleva S, Melnyk S, Pavliv O, Pogribny I, Jill James S. {{Overexpression of LINE-1 Retrotransposons in Autism Brain}}. {Mol Neurobiol}. 2017.
Long interspersed nuclear elements-1 (LINE-1 or L1) are mobile DNA sequences that are capable of duplication and insertion (retrotransposition) within the genome. Recently, retrotransposition of L1 was shown to occur within human brain leading to somatic mosaicism in hippocampus and cerebellum. Because unregulated L1 activity can promote genomic instability and mutagenesis, multiple mechanisms including epigenetic chromatin condensation have evolved to effectively repress L1 expression. Nonetheless, L1 expression has been shown to be increased in patients with Rett syndrome and schizophrenia. Based on this evidence and our reports of oxidative stress and epigenetic dysregulation in autism cerebellum, we sought to determine whether L1 expression was increased in autism brain. The results indicated that L1 expression was significantly elevated in the autism cerebellum but not in BA9, BA22, or BA24. The binding of repressive MeCP2 and histone H3K9me3 to L1 sequences was significantly lower in autism cerebellum suggesting that relaxation of epigenetic repression may have contributed to increased expression. Further, the increase in L1 expression was inversely correlated with glutathione redox status consistent with reports indicating that L1 expression is increased under pro-oxidant conditions. Finally, the expression of transcription factor FOXO3, sensor of oxidative stress, was significantly increased and positively associated with L1 expression and negatively associated with glutathione redox status. While these novel results are an important first step, future understanding of the contribution of elevated L1 expression to neuronal CNVs and genomic instability in autism will depend on emerging cell-specific genomic technologies, a challenge that warrants future investigation.
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11. Wadsworth HM, Maximo JO, Lemelman AR, Clayton K, Sivaraman S, Deshpande HD, Ver Hoef L, Kana RK. {{The Action Imitation network and motor imitation in children and adolescents with autism}}. {Neuroscience}. 2017; 343: 147-56.
While deficits in imitation had been reported in children with autism spectrum disorder (ASD), its exact nature remains unclear. A dysfunction in mirroring mechanisms (through action imitation) has been proposed by some studies to explain this, although some recent evidence points against this hypothesis. The current study used behavior and functional MRI to examine the integrated functioning of the regions that are considered part of the Action Imitation network (AIN) in children and adolescents with ASD during a motor imitation task. Fourteen ASD and 15 age-and-IQ-matched typically developing (TD) children were asked to imitate a series of hand gestures in the MRI scanner. Intact performance on imitation (accurate imitation of hand gestures outside the scanner) in both ASD and TD groups was accompanied by significantly lower activity in ASD participants, relative to TD, in right angular gyrus, precentral gyrus, and left middle cingulate. In addition, autism traits were found to be significantly correlated with activation in the right angular gyrus. Overall, the findings of this study support the role of AIN in imitation and a potential difference in the recruitment of this network in ASD children.
