1. Allen H. {{Bad Mothers and Monstrous Sons: Autistic Adults, Lifelong Dependency, and Sensationalized Narratives of Care}}. {J Med Humanit};2016 (Oct 20)
Sensationalized representations of autistic families in film and other media frequently feature violent encounters between mothers and sons. This essay analyzes two media stories and three films that suggest how limited-and therefore misleading-popular representations of the autism family are. Except for one of the films, these representations blame the problem of adult autistic dependency on either monstrous autism or bad mothering. Doing so elides collective social responsibility for autism care and denies the reality that autistic adults continue to have complex dependency needs that families cannot always meet. Narratives that sensationalize youth and adults with autism or scapegoat their maternal caregivers also diminish opportunities for social inclusion and for autistic people to live fully and dependently.
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2. Boshoff K, Gibbs D, Phillips RL, Wiles L, Porter L. {{Parents’ voices: ‘why and how we advocate’. A meta-synthesis of parents’ experiences of advocating for their child with autism spectrum disorder}}. {Child Care Health Dev};2016 (Nov);42(6):784-797.
Parenting a child with autism spectrum disorder (ASD) can be stressful, and accessing services can add to this stress. Self-efficacy, agency and advocacy are important for parents when accessing and using services. To develop insight into parental advocacy, a meta-synthesis was undertaken to consolidate the literature focussing on parents’ experiences of advocating for their child with ASD. A qualitative meta-synthesis was conducted. Fifteen databases were systematically searched by using key terms related to ASD, children, parents/carers, advocacy and qualitative studies. Twenty-four studies were identified and appraised using an adapted version of the Critical Appraisal Skills Programme tool. Data were synthesized into themes through the steps of review, meta-aggregation, integration and interpretation. Two overarching concepts emerged, illustrating both the challenging nature of advocacy and the associated personal and societal benefits. These two concepts are supported by eight themes: a life-long, all-encompassing challenge; advocacy as a parental coping strategy; advocacy involving working to create a future; balancing roles and needs; isolation versus support; personal impacts of advocacy; benefits of advocacy; and the barriers to advocacy. The experience of advocacy for parents with a child with ASD is complex and intensive, presenting both personal and societal benefits, as well as challenges for parents. In supporting individuals with ASD and family well-being, service providers need to have an understanding of the advocating role of parents and ensure that opportunities exist for their voices to be heard during service delivery.
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3. de Marchena A, Miller J. {{« Frank » presentations as a novel research construct and element of diagnostic decision-making in autism spectrum disorder}}. {Autism Res};2016 (Oct 21)
Many individuals with ASD have a distinctive behavioral presentation that is recognizable within moments, a phenomenon we call « frank » ASD. This phenomenon has been discussed informally for decades, perhaps as « classic » ASD; however, there is no unitary « classic » presentation, and classic autism does not seem to correspond to level of functioning. Thus, neither « frank » nor « classic » autism has been delineated or studied as a research construct. To initiate the empirical study of frank ASD, we surveyed 151 clinicians, from a range of disciplines that diagnose ASD, about this phenomenon. Respondents completed a 13-item questionnaire about frank ASD, which was analyzed using a mixed-methods approach. Ninety-seven percentage of respondents were familiar with the phenomenon. Respondents estimated that 40% of the ASD population has a frank presentation. Respondents reported the most highly specific behaviors associated with frank presentations were a general sense of impaired reciprocity, quality of eye contact, atypical vocal prosody, presence of motor mannerisms, and atypical gait or posture. In general, respondents reported detecting frank features rapidly, with the majority forming their impressions within the first ten minutes of interaction or observation. Although unstudied empirically, « frank » presentations of ASD are familiar to diagnosing clinicians, and appear to be based on behaviors both central to ASD diagnostic criteria (e.g., impaired reciprocity), and absent from diagnostic criteria (e.g., atypical gait or posture). We discuss these findings within the context of diagnostic decision-making and behavioral phenotyping of ASD. Autism Res 2016,. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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4. Flores-Pajot MC, Ofner M, Do MT, Lavigne E, Villeneuve PJ. {{Childhood autism spectrum disorders and exposure to nitrogen dioxide, and particulate matter air pollution: A review and meta-analysis}}. {Environ Res};2016 (Nov);151:763-776.
BACKGROUND AND OBJECTIVE: Genetic and environmental factors have been recognized to play an important role in autism. The possibility that exposure to outdoor air pollution increases the risk of autism spectrum disorder (ASD) has been an emerging area of research. Herein, we present a systematic review, and meta-analysis of published epidemiological studies that have investigated these associations. METHODS: We undertook a comprehensive search strategy to identify studies that investigated outdoor air pollution and autism in children. Overall, seven cohorts and five case-control studies met our inclusion criteria for the meta-analysis. We summarized the associations between exposure to air pollution and ASD based on the following critical exposure windows: (i) first, second and third trimester of pregnancy, (ii) entire pregnancy, and (iii) postnatal period. Random effects meta-analysis modeling was undertaken to derive pooled risk estimates for these exposures across the studies. RESULTS: The meta-estimates for the change in ASD associated with a 10mug/m3 increase in exposure in PM2.5 and 10 ppb increase in NO2 during pregnancy were 1.34 (95% CI:0.83, 2.17) and 1.05 (95% CI:0.99, 1.11), respectively. Stronger associations were observed for exposures received after birth, but these estimates were unstable as they were based on only two studies. O3 exposure was weakly associated with ASD during the third trimester of pregnancy and during the entire pregnancy, however, these estimates were also based on only two studies. CONCLUSION: Our meta-analysis support the hypothesis that exposure to ambient air pollution is associated with an increased risk of autism. Our findings should be interpreted cautiously due to relatively small number of studies, and several studies were unable to control for other key risk factors.
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5. Garman HD, Spaulding CJ, Webb SJ, Mikami AY, Morris JP, Lerner MD. {{Wanting it Too Much: An Inverse Relation Between Social Motivation and Facial Emotion Recognition in Autism Spectrum Disorder}}. {Child Psychiatry Hum Dev};2016 (Dec);47(6):890-902.
This study examined social motivation and early-stage face perception as frameworks for understanding impairments in facial emotion recognition (FER) in a well-characterized sample of youth with autism spectrum disorders (ASD). Early-stage face perception (N170 event-related potential latency) was recorded while participants completed a standardized FER task, while social motivation was obtained via parent report. Participants with greater social motivation exhibited poorer FER, while those with shorter N170 latencies exhibited better FER for child angry faces stimuli. Social motivation partially mediated the relationship between a faster N170 and better FER. These effects were all robust to variations in IQ, age, and ASD severity. These findings augur against theories implicating social motivation as uniformly valuable for individuals with ASD, and augment models suggesting a close link between early-stage face perception, social motivation, and FER in this population. Broader implications for models and development of FER in ASD are discussed.
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6. Gigonzac MA, Teodoro LS, Minasi LB, Vieira TC, da Cruz AD. {{Standardization of capillary electrophoresis for diagnosis of fragile X syndrome in the Brazilian public health system}}. {Electrophoresis};2016 (Sep 26)
Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability. The most common etiology of the syndrome is expansion and methylation of a CGG trinucleotide at chromosome region Xq27.3 involving FMR1 (fragile X mental retardation 1 gene). This disorder is commonly underdiagnosed in children and adolescents, given the high clinical variability. In Brazil, molecular diagnosis of FXS by CE does not exist in the public health system. The current standard for separation and identification of DNA fragment sizes is 50 cm CE, which is uncommon in public genotyping laboratories. This study describes the standardization of 36 cm CE for fragment analysis of samples from patients with intellectual disability suggestive of FXS. Genomic dsDNA was isolated from patients and amplified by PCR using the FMR1 AmplideX(R) Kit. It was then possible to detect changes in repeat length of FMR1, such as full mutation and premutation. Thus, the proposed standardization proved to be effective for the diagnosis of FXS, permitting suitable genetic counseling for families. Inclusion of molecular testing such as this in the Brazilian public health service bridges the gap between available technologies and effective diagnosis, universalizing access to genetic testing in central Brazil.
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7. Granich J, Dass A, Busacca M, Moore D, Anderson A, Venkatesh S, Duong T, Vellanki P, Richdale A, Trembath D, Cairns D, Marshall W, Rodwell T, Rayner M, Whitehouse AJ. {{Randomised controlled trial of an iPad based early intervention for autism: TOBY playpad study protocol}}. {BMC Pediatr};2016 (Oct 19);16(1):167.
BACKGROUND: Evidence for early intensive behavioural interventions (EIBI) by therapists as an effective treatment for children with an Autism Spectrum Disorder (ASD) is growing. High-intensity and sustained delivery of quality EIBI is expensive. The TOBY (Therapy Outcomes by You) Playpad is an App-based platform delivering EIBI to facilitate learning for young children with ASD, while enabling parents to become co-therapists. Intervention targets include increasing joint attention, imitation and communication of children with ASD. The primary aim of the study presented in this protocol is to determine the effectiveness of the TOBY App in reducing ASD symptoms when used as a complement to conventional EIBI. The secondary aim is to examine parental attributes as a result of TOBY App use. METHODS AND DESIGN: Children aged less than 4;3 years diagnosed with ASD and parents will be recruited into this single-blind, randomised controlled trial using a pragmatic approach. Eligible participants will be randomised to the treatment group ‘TOBY therapy + therapy as usual’ or, the control group ‘therapy as usual’ for six months. The treatment will be provided by the TOBY App and parent where a combination of learning environments such as on-iPad child only (solo), partner (with parent) and off-iPad – Natural Environment (with parent) Tasks will be implemented. Parents in the treatment group will participate in a TOBY training workshop. Treatment fidelity will be monitored via an App-based reporting system and parent diaries. The primary outcome measure is the Autism Treatment Evaluation Checklist. The secondary outcome measures involve diagnostics, functional and developmental assessments, including parent questionnaires at baseline (T0), three months (T1) and six months (T2). DISCUSSION: This trial will determine the effectiveness of the TOBY App as a therapeutic complement to other early interventions children with ASD receive. The trial will also determine the feasibility of a parent delivered early intervention using the iPad as an educational platform, and assess the impact of the TOBY App on parents’ self-efficacy and empowerment in an effort to reduce children’s ASD symptoms. The outcomes of this trial may have EIBI services implications for newly diagnosed children with ASD and parents. TRIAL REGISTRATION: ACTRN12614000738628 retrospectively registered on 1st of July, 2014. UTN: U1111-1158-6423.
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8. Hall A, Finch T, Kolehmainen N, James D. {{Implementing a video-based intervention to empower staff members in an autism care organization: a qualitative study}}. {BMC Health Serv Res};2016 (Oct 21);16(1):608.
BACKGROUND: Implementing good-quality health and social care requires empowerment of staff members within organizations delivering care. Video Interaction Guidance (VIG) is an intervention using positive video feedback to empower staff through reflection on practice. This qualitative study explored the implementation of VIG within an autism care organization in England, from the perspective of staff members undergoing training to deliver VIG. METHODS: Semi-structured interviews were conducted with a purposive sample of 7 participants working within the organization (5 staff undergoing training to deliver VIG; 2 senior managers influencing co-ordination of training). Participants were asked about their views of VIG and its implementation. The topic guide was informed by Normalization Process Theory (NPT). Data were analysed inductively and emerging issues were related to NPT. RESULTS: Five broad themes were identified: (1) participants reported that they and other staff did not understand VIG until they became involved, initially believing it would highlight negative rather than positive practice; (2) enthusiastic feedback from staff who had been involved seemed to encourage other staff to become involved; (3) key implementation challenges included demands of daily work and securing managers’ support; (4) ideas for future practice arising from empowerment through VIG seemed difficult to realise within an organizational culture reportedly unreceptive to creative ideas from staff; (5) individuals’ emotional responses to implementation seemed beyond the reach of NPT, which focused more upon collective processes. CONCLUSIONS: Implementation of VIG may require recognition that it is not a ‘quick fix’. Peer advocacy may be a fruitful implementation strategy. Senior managers may need to experience VIG to develop their understanding so that they can provide appropriate implementation support. NPT may lack specificity to explain how individual agency weaves with collective processes and social systems to embed innovation in routine practice. This exploratory study has provided broad insights into facilitators and barriers to the implementation of an intervention to empower staff within an autism care organization. Further research is needed into similar interventions, including a focus upon staff members’ emotional responses and resources, and how such interventions may relate to the culture of the organization in which implementation occurs.
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9. Jamison TR, Schuttler JO. {{Overview and Preliminary Evidence for a Social Skills and Self-Care Curriculum for Adolescent Females with Autism: The Girls Night Out Model}}. {J Autism Dev Disord};2016 (Oct 18)
A majority of social skills research in autism spectrum disorder (ASD) and interventions target school age males and no published studies target adolescent females with ASD or related disabilities. Females with ASD are at risk for internalizing symptoms, and experience greater challenges in socialization and communication as social demands become increasingly complex in adolescence. This paper provides a thorough description of a social skills and self-care program designed to address the specific needs of adolescent females with ASD. The approach is peer mediated and occurs within natural or community settings to facilitate generalization. Findings from program evaluation data collected across 4 years illustrate significant improvements in perceived social competence, self-perception, and quality of life and suggests the approach is feasible and social valid.
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10. Jeddi MZ, Janani L, Memari AH, Akhondzadeh S, Yunesian M. {{The role of phthalate esters in autism development: A systematic review}}. {Environ Res};2016 (Nov);151:493-504.
BACKGROUND: Available evidence implicates environmental factors in the pathogenesis of autism spectrum disorders (ASD). However, the role of specific environmental chemicals such as phthalate esters that influence ASD risk remains elusive. This paper systematically reviews published evidences on association between prenatal and/or childhood exposure to phthalate and ASD. METHODS: Studies pertaining to systematic literature search from Scopus, PubMed, PsycInfo and Web of Science prior to December 2015 were identified. The authors included studies which assessed the effect of exposure to phthalates on occurrence of ASD. This comprehensive bibliographic search identified five independent studies. Each eligible paper was summarized with respect to its methods and results with particular attention to study design and exposure assessment. Because of the heterogeneity in the type of included studies, different methods of assessing exposure to phthalates and the use of different statistics for summarizing the results, meta-analysis could not be used to combine the results of included studies. RESULTS: The results of this systematic review have revealed the limited number of studies conducted and assessed phthalate exposure. Seven studies were regarded as relevant to the objectives of this review. Two of them did not measure phthalate exposure directly and did not result in quantitative results. Out of the five studies in which phthalate exposure was mainly measured by the examining biomarkers in biological samples, two were cohort studies (one with positive results and another one with not clear association). Among the three case control studies, two of them showed a significant relation between exposure to phthalate and ASD and the last case control study had negative results. Indeed, this case control studies showed a compromised phthalate metabolite glucuronidation pathway, as a probable explanation of mechanism of the relation between phthalate exposure and ASD. CONCLUSIONS: This review reveals evidence showing a connection between exposure to phthalates and ASD. Nevertheless, further research is needed with appropriate attention to exposure assessment and relevant pre and post-natal cofounders.
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11. Kissine M, Clin E, de Villiers J. {{[Pragmatics in autism spectrum disorder: recent developments]}}. {Med Sci (Paris)};2016 (Oct);32(10):874-878.
Autism spectrum disorder (ASD) is characterized by primary pragmatic difficulties, out of step with verbal and non-verbal developmental level. This selective survey paper addresses three recent domains of research on pragmatic functions in autism. First, we provide an up-to-date discussion of how lack of sensitivity to social cues impacts early acquisition of words. Second, we review recent findings on the comprehension of non-literal language, pointing to a more refined clinical reality. Third, we describe recent developments in the study of conversation skills in autism.
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12. Krans A, Kearse MG, Todd PK. {{RAN translation from antisense CCG repeats in Fragile X Tremor/Ataxia Syndrome}}. {Ann Neurol};2016 (Oct 19)
OBJECTIVE: Repeat associated non-AUG (RAN) translation drives production of toxic proteins from pathogenic repeat sequences in multiple untreatable neurodegenerative disorders. Fragile X-associated tremor/ataxia syndrome (FXTAS) is one such condition, resulting from a CGG trinucleotide repeat expansion in the 5′ leader sequence of the FMR1 gene. RAN proteins from the CGG repeat accumulate in ubiquitinated inclusions in FXTAS patient brains and elicit toxicity. In addition to the CGG repeat, an antisense mRNA containing a CCG repeat is also transcribed from the FMR1 locus. We evaluated whether this antisense CCG repeat supports RAN translation and contributes to pathology in FXTAS patients. METHODS: We generated a series of CCG RAN translation specific reporters and utilized them to measure RAN translation from CCG repeats in multiple reading frames in transfected cells. We also developed antibodies against predicted CCG RAN proteins and used immunohistochemistry and immunofluorescence on FXTAS patient tissues to measure their accumulation and distribution. RESULTS: RAN translation from CCG repeats is supported in all three potential reading frames, generating polyproline, polyarginine, and polyalanine proteins, respectively. Their production occurs whether or not the natural AUG start upstream of the repeat in the proline reading frame is present. All three frames show greater translation at larger repeat sizes. Antibodies targeted to the antisense FMR polyproline and polyalanine proteins selectively stain nuclear and cytoplasmic aggregates in FXTAS patients and colocalize with ubiquitinated neuronal inclusions. INTERPRETATION: RAN translation from antisense CCG repeats generates novel proteins that accumulate in ubiquitinated inclusions in FXTAS patients. This article is protected by copyright. All rights reserved.
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13. Kuzmanovic B, Rigoux L, Vogeley K. {{Brief Report: Reduced Optimism Bias in Self-Referential Belief Updating in High-Functioning Autism}}. {J Autism Dev Disord};2016 (Oct 18)
Previous research has demonstrated irrational asymmetry in belief updating: people tend to take into account good news and neglect bad news. Contradicting formal learning principles, belief updates were on average larger after better-than-expected information than after worse-than-expected information. In the present study, typically developing subjects demonstrated this optimism bias in self-referential judgments. In contrast, adults with high-functioning autism spectrum disorder (ASD) were significantly less biased when updating self-referential beliefs (each group n = 21, matched for age, gender and IQ). These findings indicate a weaker influence of self-enhancing motives on prospective judgments in ASD. Reduced susceptibility to emotional and motivational biases in reasoning in ASD could elucidate impairments of social cognition, but may also confer important cognitive benefits.
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14. Larsen E, Menashe I, Ziats MN, Pereanu W, Packer A, Banerjee-Basu S. {{A systematic variant annotation approach for ranking genes associated with autism spectrum disorders}}. {Mol Autism};2016;7:44.
BACKGROUND: The search for genetic factors underlying autism spectrum disorders (ASD) has led to the identification of hundreds of genes containing thousands of variants that differ in mode of inheritance, effect size, frequency, and function. A major challenge involves assessing the collective evidence in an unbiased, systematic manner for their functional relevance. METHODS: Here, we describe a scoring algorithm for prioritization of candidate genes based on the cumulative strength of evidence for each ASD-associated variant cataloged in AutDB (also known as SFARI Gene). We retrieved data from 889 publications to generate a dataset of 2187 rare and 711 common variants distributed across 461 genes implicated in ASD. Each individual variant was manually annotated with multiple attributes extracted from the original report, followed by score assignment using a set of standardized parameters yielding a single score for each gene. RESULTS: There was a wide variation in scores; SHANK3, CHD8, and ADNP had distinctly higher scores than all other genes in the dataset. Our gene scores were significantly correlated with other recently published rankings of ASD genes (RSpearman = 0.40-0.63; p< 0.0001), providing support for our scoring algorithm. CONCLUSIONS: This new resource, which is freely available, for the first time aggregates on one-platform variants identified from various study types (simplex, multiplex, multigenerational, and consanguineous families), from both common and rare variants, and also incorporates their putative functional consequences to arrive at a genetically and biologically driven ranking scheme. This work represents a major step in moving from simply cataloging autism variants to using data-driven approaches to gain insight into their significance. Lien vers le texte intégral (Open Access ou abonnement)
15. Lonnqvist L, Loukusa S, Hurtig T, Makinen L, Siipo A, Vayrynen E, Palo P, Laukka S, Mammela L, Mattila ML, Ebeling H. {{How young adults with autism spectrum disorder watch and interpret pragmatically complex scenes}}. {Q J Exp Psychol (Hove)};2016 (Oct 19):1-16.
The aim of the current study was to investigate subtle characteristics of social perception and interpretation in high-functioning individuals with autism spectrum disorders (ASDs), and to study the relation between watching and interpreting. As a novelty, we used an approach that combined moment-by-moment eye tracking and verbal assessment. Sixteen young adults with ASD and 16 neurotypical control participants watched a video depicting a complex communication situation while their eye movements were tracked. The participants also completed a verbal task with questions related to the pragmatic content of the video. We compared verbal task scores and eye movements between groups, and assessed correlations between task performance and eye movements. Individuals with ASD had more difficulty than the controls in interpreting the video, and during two short moments there were significant group differences in eye movements. Additionally, we found significant correlations between verbal task scores and moment-level eye movement in the ASD group, but not among the controls. We concluded that participants with ASD had slight difficulties in understanding the pragmatic content of the video stimulus and attending to social cues, and that the connection between pragmatic understanding and eye movements was more pronounced for participants with ASD than for neurotypical participants.
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16. Malkki H. {{Neurodevelopmental disorders: Maternal antibodies induce autism-like phenotype in mice}}. {Nat Rev Neurol};2016 (Oct 21)
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17. Morris SM, Acosta MT, Garg S, Green J, Huson S, Legius E, North KN, Payne JM, Plasschaert E, Frazier TW, Weiss LA, Zhang Y, Gutmann DH, Constantino JN. {{Disease Burden and Symptom Structure of Autism in Neurofibromatosis Type 1: A Study of the International NF1-ASD Consortium Team (INFACT)}}. {JAMA Psychiatry};2016 (Oct 19)
Importance: Recent reports have demonstrated a higher incidence of autism spectrum disorder (ASD) and substantially elevated autistic trait burden in individuals with neurofibromatosis type 1 (NF1). However, important discrepancies regarding the distribution of autistic traits, sex predominance, and association between ASD symptoms and attentional problems have emerged, and critical features of the ASD phenotype within NF1 have never been adequately explored. Establishing NF1 as a monogenic cause for ASD has important implications for affected patients and for future research focused on establishing convergent pathogenic mechanisms relevant to the potential treatment targets for ASD. Objective: To characterize the quantitative autistic trait (QAT) burden in a pooled NF1 data set. Design, Setting, and Participants: Anonymized, individual-level primary data were accumulated from 6 tertiary referral centers in the United States, Belgium, United Kingdom, and Australia. A total of 531 individuals recruited from NF1 clinical centers were included in the study. Main Outcomes and Measures: Distribution of ASD traits (Social Responsiveness Scale, second edition [SRS-2], with T scores of >/=75 associated with a categorical ASD diagnosis); attention-deficit/hyperactivity disorder (ADHD) traits (4 versions of Conners Rating Scale, with T scores of >/=65 indicating clinically significant ADHD symptoms); ASD symptom structure, latent structure, base rate derived from mixture modeling; and familiality. Results: Of the 531 patients included in the analysis, 247 were male (46.5%); median age was 11 years (range, 2.5-83.9) years. QAT scores were continuously distributed and pathologically shifted; 13.2% (95% CI, 10.3%-16.1%) of individuals scored within the most severe range (ie, above the first percentile of the general population distribution) in which the male to female ratio was markedly attenuated (1.6:1) relative to idiopathic ASD. Autistic symptoms in this NF1 cohort demonstrated a robust unitary factor structure, with the first principal component explaining 30.9% of the variance in SRS-2 scores, and a strong association with ADHD symptoms (r = 0.61). Within-family correlation for QAT burden (intraclass correlation coefficient, 0.73 in NF1-affected first-degree relatives) exceeded that observed in the general population and ASD family samples. Conclusions and Relevance: This study provides confirmation that the diversity of mutations that give rise to NF1 function as quantitative trait loci for ASD. Moreover, the within-family correlation implicates a high degree of mutational specificity for this associated phenotype. Clinicians should be alerted to the increased frequency of this disabling comorbidity, and the scientific community should be aware of the potential for this monogenic disorder to help elucidate the biological features of idiopathic autism.
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18. Oien RA, Hart L, Schjolberg S, Wall CA, Kim ES, Nordahl-Hansen A, Eisemann MR, Chawarska K, Volkmar FR, Shic F. {{Parent-Endorsed Sex Differences in Toddlers with and Without ASD: Utilizing the M-CHAT}}. {J Autism Dev Disord};2016 (Oct 18)
Sex differences in typical development can provide context for understanding ASD. Baron-Cohen (Trends Cogn Sci 6(6):248-254, 2002) suggested ASD could be considered an extreme expression of normal male, compared to female, phenotypic profiles. In this paper, sex-specific M-CHAT scores from N = 53,728 18-month-old toddlers, including n = 185 (32 females) with ASD, were examined. Results suggest a nuanced view of the « extreme male brain theory of autism ». At an item level, almost every male versus female disadvantage in the broader population was consistent with M-CHAT vulnerabilities in ASD. However, controlling for total M-CHAT failures, this male disadvantage was more equivocal and many classically ASD-associated features were found more common in non-ASD. Within ASD, females showed relative strengths in joint attention, but impairments in imitation.
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19. Powell G, Meredith Z, McMillin R, Freeman TC. {{Bayesian Models of Individual Differences: Combining Autistic Traits and Sensory Thresholds to Predict Motion Perception}}. {Psychol Sci};2016 (Oct 21)
According to Bayesian models, perception and cognition depend on the optimal combination of noisy incoming evidence with prior knowledge of the world. Individual differences in perception should therefore be jointly determined by a person’s sensitivity to incoming evidence and his or her prior expectations. It has been proposed that individuals with autism have flatter prior distributions than do nonautistic individuals, which suggests that prior variance is linked to the degree of autistic traits in the general population. We tested this idea by studying how perceived speed changes during pursuit eye movement and at low contrast. We found that individual differences in these two motion phenomena were predicted by differences in thresholds and autistic traits when combined in a quantitative Bayesian model. Our findings therefore support the flatter-prior hypothesis and suggest that individual differences in prior expectations are more systematic than previously thought. In order to be revealed, however, individual differences in sensitivity must also be taken into account.
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20. Stewart E, Cancilliere MK, Freeman J, Wellen B, Garcia A, Sapyta J, Franklin M. {{Elevated Autism Spectrum Disorder Traits in Young Children with OCD}}. {Child Psychiatry Hum Dev};2016 (Dec);47(6):993-1001.
Studies have shown a high prevalence of autistic spectrum traits in both children and adults with psychiatric disorders; however the prevalence rate has not yet been investigated in young children with OCD. The aim of the current study was to (1) determine whether ASD traits indicated by the Social Communication Questionnaire (SCQ) and the Social Responsiveness Scale (SRS) were elevated in young children with OCD who do not have a specific ASD diagnosis and (2) determine if ASD traits were associated with OCD severity. Participants (N = 127) were children ages 5-8 years enrolled in the pediatric obsessive-compulsive disorder treatment study for young children (POTS Jr.). Results indicated that the SRS showed elevated autistic traits in the sample and was associated with OCD severity whereas the SCQ did not indicate heightened ASD symptoms. Implications of these results are discussed.
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21. Verhaeghe L, Dereu M, Warreyn P, De Groote I, Vanhaesebrouck P, Roeyers H. {{Erratum to: Extremely Preterm Born Children at Very High Risk for Developing Autism Spectrum Disorder}}. {Child Psychiatry Hum Dev};2016 (Dec);47(6):1009.
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22. Walker SJ, Beavers DP, Fortunato J, Krigsman A. {{A Putative Blood-Based Biomarker for Autism Spectrum Disorder-Associated Ileocolitis}}. {Sci Rep};2016 (Oct 21);6:35820.
Gastrointestinal symptoms are common in children with autism spectrum disorder (ASD). A significant proportion of children with ASD and gastrointestinal symptoms have histologic evidence of ileocolitis (inflammation of the terminal ileum and/or colon). We previously reported the molecular characterization of gastrointestinal biopsy tissue from ASD children with ileocolitis (ASDIC+) compared to anatomically similar inflamed tissue from typically developing children with inflammatory bowel disease (IBD; i.e. Crohn’s disease or ulcerative colitis) and typically developing children with gastrointestinal symptoms but no evidence of gastrointestinal mucosal inflammation (TDIC-). ASDIC+ children had a gene expression profile that, while primarily overlapping with known IBD, had distinctive differences. The present study confirms these findings and replicates this molecular characterization in a second cohort of cases (ASDIC+) and controls (TDIC-). In these two separate case/control mucosal-based cohorts, we have demonstrated overlap of 59 differentially expressed transcripts (DETs) unique to inflamed ileocolonic tissue from symptomatic ASDIC+ children. We now report that 9 of these 59 transcripts are also differentially expressed in the peripheral blood of the second cohort of ASDIC+ children. This set of transcripts represents a putative blood-based biomarker for ASD-associated ileocolonic inflammation.
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23. Xie N, Gong H, Suhl JA, Chopra P, Wang T, Warren ST. {{Reactivation of FMR1 by CRISPR/Cas9-Mediated Deletion of the Expanded CGG-Repeat of the Fragile X Chromosome}}. {PLoS One};2016;11(10):e0165499.
Fragile X syndrome (FXS) is a common cause of intellectual disability that is most often due to a CGG-repeat expansion mutation in the FMR1 gene that triggers epigenetic gene silencing. Epigenetic modifying drugs can only transiently and modestly induce FMR1 reactivation in the presence of the elongated CGG repeat. As a proof-of-principle, we excised the expanded CGG-repeat in both somatic cell hybrids containing the human fragile X chromosome and human FXS iPS cells using the CRISPR/Cas9 genome editing. We observed transcriptional reactivation in approximately 67% of the CRISPR cut hybrid colonies and in 20% of isolated human FXS iPSC colonies. The reactivated cells produced FMRP and exhibited a decline in DNA methylation at the FMR1 locus. These data demonstrate the excision of the expanded CGG-repeat from the fragile X chromosome can result in FMR1 reactivation.
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24. Yang Y, Kucukkal TG, Li J, Alexov E, Cao W. {{Binding Analysis of Methyl-CpG Binding Domain of MeCP2 and Rett Syndrome Mutations}}. {ACS Chem Biol};2016 (Oct 21);11(10):2706-2715.
Methyl-CpG binding protein 2 (MeCP2) binds to methylated cytosine in CpG island through its methyl-CpG binding domain (MBD). Here, the effects of the Rett syndrome-causing missense mutations on binding affinity of MBD to cytosine (C), methylcytosine (mC), hydroxymethylcytosine (hmC), formylcytosine (fC), and carboxylcytosine (caC) in CpG dinucleotide are investigated. MeCP2-MBD binds to mC-containing variants of double stranded CpG stronger than any other cytosine modified CpG with the strongest affinity to mC/mC. Thirteen MBD missense mutations show reduced binding affinity for mC/mC ranging with a 2-fold decrease for T158M to 88-fold for R111G. The binding affinities of these mutants to C/C are also reduced to various degrees except for T158M. Consistent with free energy perturbation analysis, correlation of binding affinity with protein unfolding allows for grouping mutations into three clusters. Correlation of the first cluster includes mutations that have a higher tendency to unfold and have lesser affinity to mC/mC and C/C. Mutations in the second cluster have similar structural stability but various affinities to mC/mC and C/C. R111G and A140V belong to the third cluster in which the loss of protein flexibility may underlie their reduction in binding affinity to mC/mC and C/C. Most notably, R111 emerges as the key structural element that modulates the specific contacts with mCpG. Implications of the results for the mCpG binding mechanism of MeCP2-MBD are discussed. These analyses provide new insights on the structure and function relationships in MeCP2-MBD and offer new clues to their roles in the pathology of Rett syndrome.
