1. Chen Y, Yu J, Niu Y, Qin D, Liu H, Li G, Hu Y, Wang J, Lu Y, Kang Y, Jiang Y, Wu K, Li S, Wei J, He J, Wang J, Liu X, Luo Y, Si C, Bai R, Zhang K, Liu J, Huang S, Chen Z, Wang S, Chen X, Bao X, Zhang Q, Li F, Geng R, Liang A, Shen D, Jiang T, Hu X, Ma Y, Ji W, Sun YE. {{Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys}}. {Cell};2017 (May 18);169(5):945-955.e910.
Gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. Here, we report detailed genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which is caused by loss-of-function mutations in the human MECP2 gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a disease of females. Through a battery of behavioral analyses, including primate-unique eye-tracking tests, in combination with brain imaging via MRI, we found a series of physiological, behavioral, and structural abnormalities resembling clinical manifestations of RTT. Moreover, blood transcriptome profiling revealed that mutant monkeys resembled RTT patients in immune gene dysregulation. Taken together, the stark similarity in phenotype and/or endophenotype between monkeys and patients suggested that gene-edited RTT founder monkeys would be of value for disease mechanistic studies as well as development of potential therapeutic interventions for RTT.
Lien vers le texte intégral (Open Access ou abonnement)
2. Failla MD, Moana-Filho EJ, Essick GK, Baranek GT, Rogers BP, Cascio CJ. {{Initially intact neural responses to pain in autism are diminished during sustained pain}}. {Autism};2017 (May 01):1362361317696043.
Pain assessments typically depend on self-report of the pain experience. Yet, in individuals with autism spectrum disorders, this can be an unreliable due to communication difficulties. Importantly, observations of behavioral hypo- and hyperresponsivity to pain suggest altered pain sensitivity in autism spectrum disorder. Neuroimaging may provide insight into mechanisms underlying pain behaviors. The neural pain signature reliably responds to painful stimulation and is modulated by other outside regions, affecting the pain experience. In this first functional magnetic resonance imaging study of pain in autism spectrum disorder, we investigated neural responses to pain in 15 adults with autism spectrum disorder relative to a typical comparison group (n = 16). We explored temporal and spatial properties of the neural pain signature and its modulators during sustained heat pain. The two groups had indistinguishable pain ratings and neural pain signature responses during acute pain; yet, we observed strikingly reduced neural pain signature response in autism spectrum disorder during sustained pain and after stimulus offset. The posterior cingulate cortex, a neural pain signature modulating region, mirrored this late signal reduction in autism spectrum disorder. Intact early responses, followed by diminished late responses to sustained pain, may reflect altered pain coping or evaluation in autism spectrum disorder. Evidence of a dichotomous neural response to initial versus protracted pain may clarify the coexistence of both hypo- and hyperresponsiveness to pain in autism spectrum disorder.
Lien vers le texte intégral (Open Access ou abonnement)
3. Johannessen J, Naerland T, Hope S, Torske T, Hoyland AL, Strohmaier J, Heiberg A, Rietschel M, Djurovic S, Andreassen OA. {{Parents’ Attitudes toward Clinical Genetic Testing for Autism Spectrum Disorder-Data from a Norwegian Sample}}. {Int J Mol Sci};2017 (May 18);18(5)
Clinical genetic testing (CGT) of children with autism spectrum disorder (ASD) may have positive and negative effects. Knowledge about parents’ attitudes is needed to ensure good involvement of caregivers, which is crucial for accurate diagnosis and effective clinical management. This study aimed to assess parents’ attitudes toward CGT for ASD. Parent members of the Norwegian Autism Society were given a previously untested questionnaire and 1455 answered. Linear regression analyses were conducted to evaluate contribution of parent and child characteristics to attitude statements. Provided it could contribute to a casual explanation of their child’s ASD, 76% would undergo CGT. If it would improve the possibilities for early interventions, 74% were positive to CGT. Between 49-67% agreed that CGT could have a negative impact on health insurance, increase their concern for the child’s future and cause family conflicts. Parents against CGT (9%) were less optimistic regarding positive effects, but not more concerned with negative impacts. The severity of the children’s ASD diagnosis had a weak positive association with parent’s positive attitudes to CGT (p-values range from <0.001 to 0.975). Parents prefer that CGT is offered to those having a child with ASD (65%), when the child's development deviates from normal (48%), or before pregnancy (36%). A majority of the parents of children with ASD are positive to CGT due to possibilities for an etiological explanation. Lien vers le texte intégral (Open Access ou abonnement)
4. Lange S, Rehm J, Anagnostou E, Popova S. {{Prevalence of Externalizing Disorders and Autism Spectrum Disorder among Children with Fetal Alcohol Spectrum Disorder: Systematic Review and Meta-analysis}}. {Biochem Cell Biol};2017 (May 18)
Due to their central nervous system impairments, children with Fetal Alcohol Spectrum Disorder (FASD) commonly exhibit externalizing behaviours such as hyperactivity, impulsivity, and/or delinquency. The purpose of the current study was to estimate the prevalence of neurodevelopmental disorders with prominent externalizing behaviours, namely Attention-Deficit Hyperactivity Disorder (ADHD), Conduct Disorder (CD), Oppositional Defiant Disorder (ODD), as well as Autism Spectrum Disorder (ASD) among children with FASD. A comprehensive systematic literature search was performed, followed by disorder-specific random-effects meta-analyses. Of the disorders investigated, ADHD was found to be the most common co-morbid disorder among children with FASD (52.9%), followed by ODD (12.9%), CD (7.0%), and ASD (2.6%). When compared to the general population of the United States, these rates are notably higher: 15-times higher for ADHD, two-times higher for ASD, three-times higher for CD, and five-times higher for ODD. The results call attention to the need for identifying a distinct neurodevelopmental profile to aid in the accurate identification of children with FASD and the discrimination of FASD from certain idiopathic neurodevelopmental disorders.
Lien vers le texte intégral (Open Access ou abonnement)
5. Louzolo A, Gustavsson P, Tigerstrom L, Ingvar M, Olsson A, Petrovic P. {{Delusion-proneness displays comorbidity with traits of autistic-spectrum disorders and ADHD}}. {PLoS One};2017;12(5):e0177820.
There is an increasing body of evidence suggesting a significant comorbidity between psychotic disorders such as schizophrenia and attention-deficit/hyperactivity disorder (ADHD) or autism-spectrum disorders (ASD). Recently, research on psychosis-proneness in otherwise healthy individuals has been a promising way to better understand the mechanisms underlying psychosis. As both ADHD and ASD symptoms show a normal distribution in the general population, such trait comorbidity may confound studies on psychosis-proneness. Thus, understanding the extent to which psychosis-proneness relates to ADHD and ASD symptoms in healthy subjects is crucial for studies focusing on at-risk or psychosis-prone populations. In the present paper we tested the robustness of overlap between psychosis-proneness and ADHD/ASD symptoms, by studying correlations between the scores of three commonly-used questionnaires assessing delusion-proneness (Peters’ Delusion Inventory), ADHD tendencies (Adult ADHD Self-Report Scale) and ASD tendencies (Autism Quotient), on a large sample of healthy individuals (n = 925) using raw scores, prototypical questions and a factor analysis. The results showed consistently positive correlations between psychosis-proneness and ADHD-, as well as ASD-symptoms. While the effect was weak for ASD, it was moderate for ADHD. The findings support the idea that when investigating psychosis-proneness it is crucial to also take ADHD- and ASD-tendencies into account, in order to conclude that the reported results in a given study are specific to psychosis-proneness. The observed trait correlations also suggest a common pathway in the underlying information processing of these states.
Lien vers le texte intégral (Open Access ou abonnement)
6. Malcolm R, Ecks S, Pickersgill M. {{‘It just opens up their world’: autism, empathy, and the therapeutic effects of equine interactions}}. {Anthropol Med};2017 (May 17):1-15.
Experiences of autism-spectrum disorder are now increasingly studied by social scientists. Human-animal relations have also become a major focus of social inquiry in recent years. Examining horse-assisted therapy for autistic spectrum disorders, this is the first paper that brings these fields together. Drawing on participant observation and interviews at a UK horse therapy Centre, this article examines how staff and the parents of riders account for the successes and limitations of equine therapy. To the respondents, horses ‘open up’ autistic children and make possible interactions that seemed impossible before. Horses were regarded as facilitating the emergence of apparently social behaviours, which included eye contact, pointing, and speech. Three key explanations emerged for therapeutic success: the sensorial, embodied experience of riding the horse; the specific movements and rhythms of the horse; and, the ‘personality’ of the horse. Equine therapy can be regarded as enabling a form of multispecies intersubjectivity, with the resonance between rider and horse seeming to make possible a new attunement between humans. Practices of equine therapy, and perceptions of its efficacy, serve in turn to attune social scientists to a version of empathy constituted through lively and sensorial interactions, as opposed to one that is restricted to particular kinds of humans.
Lien vers le texte intégral (Open Access ou abonnement)
7. Maras KL, Crane L, Mulcahy S, Hawken T, Cooper P, Wurtzel D, Memon A. {{Brief Report: Autism in the Courtroom: Experiences of Legal Professionals and the Autism Community}}. {J Autism Dev Disord};2017 (May 18)
Online surveys were used to sample the views of judges, barristers and solicitors (n = 33) about their engagement with autistic individuals in criminal courts in England and Wales. Despite an understanding of some of the difficulties experienced by individuals with autism, and the adjustments suitable for supporting them, legal professionals reported constraints arising from a lack of understanding by others within the criminal justice system. These results are considered alongside the views and perspectives of autistic adults (n = 9) and parents of children on the autism spectrum (n = 19), who had encountered the criminal courts as witnesses or defendants and were largely dissatisfied with their experiences. Training, understanding and the provision of appropriate adjustments were identified as key issues by all respondent groups.
Lien vers le texte intégral (Open Access ou abonnement)
8. Milne E, Dickinson A, Smith R. {{Adults with autism spectrum conditions experience increased levels of anomalous perception}}. {PLoS One};2017;12(5):e0177804.
Autism spectrum condition (ASC) is characterised by differences in social interaction and behavioural inflexibility. In addition to these core symptoms, atypical sensory responses are prevalent in the ASC phenotype. Here we investigated anomalous perception, i.e. hallucinatory and/or out of body experiences in adults with ASC. Thirty participants with an ASC diagnosis and thirty neurotypical controls completed the Cardiff Anomalous Perception Scale (CAPS) and the Social Responsiveness Scale (SRS-2). The CAPS is a 32-item questionnaire that asks participants to indicate whether or not they experience a range of anomalous and out of body experiences, and to rate how intrusive and distressing these experiences are. The SRS-2 asks participants to rate the extent to which they identify with a series of 65 statements that describe behaviours associated with the autism phenotype. We found that total CAPS score was significantly higher in the participants with ASC (mean = 14.8, S.D. = 7.9) than the participants without ASC (mean = 3.6, S.D. = 4.1). In addition, the frequency of anomalous perception, the level of distraction and the level of distress associated with the experience were significantly increased in participants with ASC. Importantly, both the frequency of anomalous perceptual experiences and the level of distress caused by anomalous perception in this sample of adults with ASC were very similar to that reported previously in a sample of non-autistic participants who were being treated in hospital for a current psychotic episode. These data indicate that anomalous perceptual experiences are common in adults with ASC and are associated with a high level of distress. The origins of anomalous perception in ASC and the implication of this phenomenon are considered.
Lien vers le texte intégral (Open Access ou abonnement)
9. Murata E, Mohri I, Kato-Nishimura K, Iimura J, Ogawa M, Tachibana M, Ohno Y, Taniike M. {{Evaluation of behavioral change after adenotonsillectomy for obstructive sleep apnea in children with autism spectrum disorder}}. {Res Dev Disabil};2017 (Jun);65:127-139.
BACKGROUND AND OBJECTIVE: Obstructive sleep apnea (OSA) may affect daily cognitive functioning in children. The aims of our study were two-fold. The first aim was to detect, using the Child Behavior Checklist (CBCL), whether adenotonsillectomy (AT) for the treatment of OSA improved the behavior of children with autism spectrum disorder (ASD). The second aim was to identify characteristics for behavioral improvement following the treatment of OSA in these children with ASD. METHODS: The behaviors of ASD children aged 5-14 years diagnosed as having OSA (n=30) were evaluated using CBCL before and after AT. CBCL evaluation of ASD children without OSA at two time points with the same interval served as a control (n=24). We statistically examined the two groups. In addition, we conducted a paired t-test to assess changes in CBCL Tscores between the improved group and unchanged/deteriorated group to identify characteristics that may affect behavioral changes following OSA treatment. RESULTS: After AT, T-scores of the CBCL scales were significantly improved in the OSA group, but no change was observed in the control. A paired t-test revealed that the improved group had significantly higher scores on the CBCL pre-AT than the unchanged/deteriorated group in ASD children with OSA after OSA treatment. CONCLUSIONS: Behavioral problems were significantly improved following AT in ASD children with OSA. Early detection and treatment of children with OSA is essential to prevent behavioral problems and to support mental development.
Lien vers le texte intégral (Open Access ou abonnement)
10. Narasingharao K, Pradhan B, Navaneetham J. {{Efficacy of Structured Yoga Intervention for Sleep, Gastrointestinal and Behaviour Problems of ASD Children: An Exploratory Study}}. {J Clin Diagn Res};2017 (Mar);11(3):Vc01-vc06.
INTRODUCTION: Autism Spectrum Disorder (ASD) is a neuro developmental disorder which appears at early childhood age between 18 and 36 months. Apart from behaviour problems ASD children also suffer from sleep and Gastrointestinal (GI) problems. Major behaviour problems of ASD children are lack of social communication and interaction, less attention span, repetitive and restrictive behaviour, lack of eye to eye contact, aggressive and self-injurious behaviours, sensory integration problems, motor problems, deficiency in academic activities, anxiety and depression etc. Our hypothesis is that structured yoga intervention will brings significant changes in the problems of ASD children. AIM: The aim of this study was to find out efficacy of structured yoga intervention for sleep problems, gastrointestinal problems and behaviour problems of ASD children. MATERIALS AND METHODS: It was an exploratory study with pre-test and post-test control design. Three sets of questionnaires having 61 questions developed by researchers were used to collect data pre and post yoga intervention. Questionnaires were based on three problematic areas of ASD children as mentioned above and were administered to parents by teachers under the supervision of researcher and clinical psychologists. Experimental group was given yoga intervention for a period of 90 days and control group continued with school curriculum. RESULTS: Both children and parents participated in this intervention. Significant changes were seen post yoga intervention in three areas of problems as mentioned above. Statistical analysis also showed significance value of 0.001 in the result. CONCLUSION: Structured yoga intervention can be conducted for a large group of ASD children with parent’s involvement. Yoga can be used as alternative therapy to reduce the severity of symptoms of ASD children.
Lien vers le texte intégral (Open Access ou abonnement)
11. Nottingham CL, Vladescu JC, Kodak T, Kisamore AN. {{Incorporating multiple secondary targets into learning trials for individuals with autism spectrum disorder}}. {J Appl Behav Anal};2017 (May 17)
The current study examined the outcome of presenting multiple secondary targets in learning trials for individuals with autism spectrum disorder. We compared conditions in which (a) a secondary target was presented in the antecedent and consequence of trials, (b) two secondary targets were presented in the consequence of trials, (c) one secondary target was presented in the consequence of each trial, and (d) no additional targets were presented trials. The participants acquired the majority of secondary targets. Presenting one or multiple secondary targets per trial, regardless of the location of these secondary targets, increased the efficiency of instruction in comparison to a condition with no secondary target.
Lien vers le texte intégral (Open Access ou abonnement)
12. Ousley O, Evans AN, Fernandez-Carriba S, Smearman EL, Rockers K, Morrier MJ, Evans DW, Coleman K, Cubells J. {{Examining the Overlap between Autism Spectrum Disorder and 22q11.2 Deletion Syndrome}}. {Int J Mol Sci};2017 (May 18);18(5)
22q11.2 deletion syndrome (22q11.2DS) is a genomic disorder reported to associate with autism spectrum disorders (ASDs) in 15-50% of cases; however, others suggest that individuals with 22q11.2DS present psychiatric or behavioral features associated with ASDs, but do not meet full criteria for ASD diagnoses. Such wide variability in findings may arise in part due to methodological differences across studies. Our study sought to determine whether individuals with 22q11.2DS meet strict ASD diagnostic criteria using research-based guidelines from the Collaborative Programs of Excellence in Autism (CPEA), which required a gathering of information from three sources: the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observational Schedule (ADOS), and a clinician’s best-estimate diagnosis. Our study examined a cohort of children, adolescents, and young adults (n = 56) with 22q11.2DS, who were ascertained irrespective of parents’ behavioral or developmental concerns, and found that 17.9% (n = 10) of the participants met CPEA criteria for an ASD diagnosis, and that a majority showed some level of social-communication impairment or the presence of repetitive behaviors. We conclude that strictly defined ASDs occur in a substantial proportion of individuals with 22q11.2DS, and recommend that all individuals with 22q11.2DS be screened for ASDs during early childhood.
Lien vers le texte intégral (Open Access ou abonnement)
13. Pagan C, Goubran-Botros H, Delorme R, Benabou M, Lemiere N, Murray K, Amsellem F, Callebert J, Chaste P, Jamain S, Fauchereau F, Huguet G, Maronde E, Leboyer M, Launay JM, Bourgeron T. {{Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders}}. {Sci Rep};2017 (May 18);7(1):2096.
Autism spectrum disorders (ASD) are characterized by a wide genetic and clinical heterogeneity. However, some biochemical impairments, including decreased melatonin (crucial for circadian regulation) and elevated platelet N-acetylserotonin (the precursor of melatonin) have been reported as very frequent features in individuals with ASD. To address the mechanisms of these dysfunctions, we investigated melatonin synthesis in post-mortem pineal glands – the main source of melatonin (9 patients and 22 controls) – and gut samples – the main source of serotonin (11 patients and 13 controls), and in blood platelets from 239 individuals with ASD, their first-degree relatives and 278 controls. Our results elucidate the enzymatic mechanism for melatonin deficit in ASD, involving a reduction of both enzyme activities contributing to melatonin synthesis (AANAT and ASMT), observed in the pineal gland as well as in gut and platelets of patients. Further investigations suggest new, post-translational (reduced levels of 14-3-3 proteins which regulate AANAT and ASMT activities) and post-transcriptional (increased levels of miR-451, targeting 14-3-3zeta) mechanisms to these impairments. This study thus gives insights into the pathophysiological pathways involved in ASD.
Lien vers le texte intégral (Open Access ou abonnement)
14. Scott M, Jacob A, Hendrie D, Parsons R, Girdler S, Falkmer T, Falkmer M. {{Employers’ perception of the costs and the benefits of hiring individuals with autism spectrum disorder in open employment in Australia}}. {PLoS One};2017;12(5):e0177607.
Research has examined the benefits and costs of employing adults with autism spectrum disorder (ASD) from the perspective of the employee, taxpayer and society, but few studies have considered the employer perspective. This study examines the benefits and costs of employing adults with ASD, from the perspective of employers. Fifty-nine employers employing adults with ASD in open employment were asked to complete an online survey comparing employees with and without ASD on the basis of job similarity. The findings suggest that employing an adult with ASD provides benefits to employers and their organisations without incurring additional costs.
Lien vers le texte intégral (Open Access ou abonnement)
15. Stern YS, Maltman N, Roberts MY. {{The Influence of Maternal Pragmatics on the Language Skills of Children with Autism}}. {J Dev Behav Pediatr};2017 (May 15)
OBJECTIVE: This study examined the relationship between mothers’ pragmatics and child language in autism spectrum disorder (ASD) and non-ASD language delay (LD) mother-child dyads. METHODS: Participants consisted of 20 dyads of mothers and their toddlers aged 24 to 48 months, with ASD (n = 10) or non-ASD LD (n = 10). Groups were matched on child chronological age, language, and cognition. Maternal pragmatic language was qualified based on the degree of pragmatic violations during a semistructured interview, and was examined in relation to both child language, as measured by the Preschool Language Scale-4 and maternal use of language facilitation strategies during play. RESULTS: Lower rates of maternal pragmatic violations were associated with higher expressive language scores in children with ASD, and with higher receptive language scores for children with non-ASD LD. Within ASD dyads, maternal pragmatic violations were negatively related to mothers’ use of linguistic expansions. CONCLUSION: These findings indicate that parental pragmatics likely contribute to early language learning, and that the effects of maternal pragmatics on early language in ASD may be indirect (e.g., through parents’ use of facilitative strategies). Parent-mediated language interventions for ASD should therefore consider parent pragmatics, especially given that pragmatic differences have been identified in unaffected family members of individuals with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
16. Vojinovic D, Brison N, Ahmad S, Noens I, Pappa I, Karssen LC, Tiemeier H, van Duijn CM, Peeters H, Amin N. {{Variants in TTC25 affect autistic trait in patients with autism spectrum disorder and general population}}. {Eur J Hum Genet};2017 (May 17)
Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder with a complex genetic architecture. To identify genetic variants underlying ASD, we performed single-variant and gene-based genome-wide association studies using a dense genotyping array containing over 2.3 million single-nucleotide variants in a discovery sample of 160 families with at least one child affected with non-syndromic ASD using a binary (ASD yes/no) phenotype and a quantitative autistic trait. Replication of the top findings was performed in Psychiatric Genomics Consortium and Erasmus Rucphen Family (ERF) cohort study. Significant association of quantitative autistic trait was observed with the TTC25 gene at 17q21.2 (effect size=10.2, P-value=3.4 x 10-7) in the gene-based analysis. The gene also showed nominally significant association in the cohort-based ERF study (effect=1.75, P-value=0.05). Meta-analysis of discovery and replication improved the association signal (P-valuemeta=1.5 x 10-8). No genome-wide significant signal was observed in the single-variant analysis of either the binary ASD phenotype or the quantitative autistic trait. Our study has identified a novel gene TTC25 to be associated with quantitative autistic trait in patients with ASD. The replication of association in a cohort-based study and the effect estimate suggest that variants in TTC25 may also be relevant for broader ASD phenotype in the general population. TTC25 is overexpressed in frontal cortex and testis and is known to be involved in cilium movement and thus an interesting candidate gene for autistic trait.European Journal of Human Genetics advance online publication, 17 May 2017; doi:10.1038/ejhg.2017.82.
Lien vers le texte intégral (Open Access ou abonnement)
17. Ziegler A, Rudolph-Rothfeld W, Vonthein R. {{Genetic Testing for Autism Spectrum Disorder is Lacking Evidence of Cost-effectiveness. A Systematic Review}}. {Methods Inf Med};2017 (May 18);56(3):268-273.
BACKGROUND: Autism Spectrum Disorder (ASD) is a highly heritable neural development disorder characterized by social impairment. The earlier the diagnosis is made, the higher are the chances of obtaining relief of symptoms. A very early diagnosis uses molecular genetic tests, which are also offered commercially. OBJECTIVE: Systematic review of the economic impact of genetic tests in ASD. METHODS: We performed a systematic search of databases Pubmed, Medline, Cochrane, Econlit and the NHS Center for Reviews and Dissemination for articles in English and German from January 1, 2000 to December 31, 2015. Original articles published in peer-reviewed journals were screened in a two-step process. First, we focused our search on economic evaluations of genetic tests for ASD. Second, we searched for any economic evaluation (EE) of genetic tests. RESULTS: We identified 185 EE of genetic tests for various diseases. However, not a single EE of genetic tests has been found for ASD. The outcomes used in the EE of the genetic tests were heterogeneous, and results were generally not comparable. CONCLUSION: There is no evidence for cost-effectiveness of any genetic diagnostic test for ASD, although such genetic tests are available commercially. Cost-effectiveness analyses for genetic diagnostic tests for ASD are urgently required. There is a clear lack in research for EE of genetic tests.
